More about the Mouse

The unhappy rise of the mouse as an industrialized laboratory animal has already featured in this blog (see ‘Earth-born Companions’, 7 July 2017). Now it seems that the institution described in that post as driving and servicing this development in the UK, the Medical Research Council’s Harwell Institute in Oxfordshire (“ground breaking mammalian genetics”), is likely to close. That would end scientific research there – though not the breeding and supplying of mice to other institutions, which is a separate operation on the same site. The reason for this closure hasn’t been made public. However, there is similar news from another UK centre for research using mice, the Wellcome Sanger Institute in Cambridgeshire, which is about to close down its own mouse-breeding department (though in this case not the research itself), and for this a clear public explanation has been given: “The Sanger Institute is increasingly using alternative technologies to deliver its scientific strategy and this has led to fewer mice being needed.”

We might hope and suppose that these two decisions by notable centres for mouse research indicate a waning of professional enthusiasm for such work. And certainly there has been plenty of criticism of it in recent years. A semi-humourous branch of this criticism appears regularly in the Twitter account @justsaysinmice. Announcements in the press of exciting medical ‘breakthroughs’ (“Scientists make breakthrough with potential new tinnitus cure”, “Scientists discover ‘critical breakthrough’ in cure for baldness”) are re-posted there with the deflationary heading ‘In mice’. The Twitter account is run by a scientist who expressly does not intend it as an attack on the research itself; still, it highlights the truth that most of these ‘breakthroughs’ will remain exclusively mouse-related and not be heard of again in public.

It’s hard to know how far the scientists themselves are to blame when their work is casually bounced into human relevance like this. Some of them seem all too content to be pursuing research on mice as if it’s a goal in itself – which professionally it may well be. But perhaps it’s a point of tactics not to make that too obvious. ‘Social transmission of food safety depends on synaptic plasticity in the prefrontal cortex’ announces a recent report in a professional journal, describing research into the way mice influence each other’s choice of food with involuntary scent signals. This is not offered as a study of mouse behaviour, but as a highly technical and invasive piece of neuroscience, and you may notice the definite article – “the prefrontal cortex” – suggesting the discovery of a general truth. Even so, it soon becomes clear that we’re really just learning a bit more about mice (at their own considerable expense). At no point is any relevance to human diet proposed, and since humans are weak in scent-awareness but do have other more reliable ways of learning from each other what’s good to eat, it’s hard to see how there could be any relevance. The article illustrates the way that mice have become not so much a preliminary in medical research, as something like a surrogate for it.

No wonder, then, that one critical study of neuroscience’s preoccupation with mice has likened it to the situation in Hans Christian Anderson’s story ‘The Emperor’s New Emperor's ClothesClothes’: a kind of shared delusion or conspiracy to admire what isn’t really there. As a result of this delusion, “vast investments of both time and money” have been put into research “rarely translating into successful treatment of major disorders in humans” (aka ‘just in mice’).

We’ll come back later to that article, which is itself not quite what at first it seems. Meanwhile what needs noticing is that none of this criticism from within the profession, valuable as it may be, has any ethical dimension – at least, not one that includes the animals. There was an article in the journal Science recently (31 May issue) complaining of sexism in mouse research, and sub-headed “outdated gender stereotypes are influencing experimental design in laboratory animals.” The charge was that researchers have habitually preferred to use male animals, male mice particularly, because they believe that “circulating ovarian hormones make data from female animals messier and more variable than data from males.” In neuroscience, this preference has encouraged the view that the male brain is the standard, from which the female brain is a more or less unpredictable deviation. It’s an interesting and convincing claim, but the proposed cure for this sexism, which is naturally enough to incorporate female animals in all such studies, will evidently involve using more mice than before. Some studies would simply have to be doubled to accommodate both genders.

So although there’s a strong ethical correction being made here, the mice have no part or profit in it. That becomes especially obvious when the author, Rebecca Shansky of the Department of Psychology at Northeastern University, casually lists some of the ruthless research devices in which these mice, male or female, must participate: “tests such as the elevated plus maze [a device to measure anxiety-responses], forced swim and fear conditioning”. Many more of the like to come, then, because Dr Shansky’s mice may help her and others to break the prerogative of the man, but she won’t be helping them against the prerogative of the human. Ethically, the mice are to remain non-entities.

But then even the Sanger Institute (to return to that piece of good news for mice) doesn’t present its increased use of “alternative technologies” as an ethical advance. Although the Institute’s public statement does refer to the welfare of the mice as being put at risk by reductions in staff, and even cites the 1986 Animals (Scientific Procedures) Act in that connection, it most strangely leaves unmentioned the main long-term objective of that Act, which is exactly to reduce the numbers of animals used in research. Why isn’t the Institute taking any credit for its part in realizing this aim?

I can think of only two reasons. One is that there is no enthusiasm within the profession for the aim, and it would seem tactless therefore to celebrate what the staff and fellow-professionals will see as pure loss. (Conversely, you may recall that the CEO of Understanding Animal Research greeted the Home Office animal count of 3.7 million last year as a healthy sign of “the important contribution that the UK makes to scientific and medical advancement worldwide”: see this blog for 23 July 2018.) The other and closely-related reason is that it simply didn’t occur to the Institute to make the connection: i.e. that reducing numbers has never been a serious objective there.

Back to the emperor’s new clothes. The article in question was written by “a junior professor [Michael Yartsev] trying to learn from the lessons of the past and look into the future”. The ‘emperor’, in Yartsev’s re-telling of the tale, stands for his own chosen field of research, neuroscience; the ‘clothes’ are the research animals which are most commonly used there (what he calls “the standard model organisms”). These he lists as rats, mice, and humans.

Eh? Humans? Are even humans themselves of merely illusory usefulness as test subjects for neuroscience? No, because the Hans Anderson analogy is all wrong. Yartsev is not like the boy who uniquely spots that the emperor has nearly nothing on; quite the contrary, he shares the general confidence in those “standard model organisms” and the “great benefits” they bring. His correction, much like Rebecca Shansky’s, is only that they’re not enough. This is more or less intelligible from his title, once you know: ‘The emperor’s new wardrobe: rebalancing diversity of animal models in neuroscience research’. Not real clothes, then, but more clothes, more species, are what’s needed for progress in that looked-into future, or as he says in his junior-professorial prose, “This necessitates expanding the portfolio of utilized animal models”.

Yartsev’s keen and fresh-minded vision of the future is made all the more dismal to read by its essential conformity. The young scientist scans the whole natural world, noting its rich variety (and making clear whose it is): “Over 8 million species reside on our planet.” And he sees it all as laboratory fodder. Why, he asks, are we leaving so many of these species alone? In the case of “vocal learning”, for instance: true, we’ve branched out into the songbirds here (and how sad and ominous that word is, in this research context!), but what about bats, cetaceans, elephants, non-human primates? We’ve scarcely troubled these mammals on the subject. Nor, for this or any other purpose, do we have to take them merely as they are. It was genetic manipulation which made the mouse so variously useful, but now there are “revolutionary DNA-editing methods that can be applied to any animals”.

This vision of the future was published in the USA, where the legal and moral hindrances to animal research are very much weaker than they are in Europe; mice, after all, do not count as animals at all in the relevant legislation there (nor do “songbirds”). Still, it’s a vision that Europe’s scientists evidently share, as a report from one of their EMBO conferences – which incidentally provides a link to the Yartsev article – makes very plain. One EMBO member is quoted as saying, “For a long time, the good excuse to ignore about 99.9999% of species was that it was technically almost impossible to study them. But this is now changing.” That number is facetiously extended to four decimal points presumably to show how enormous is the variety of life that awaits our exploitation. (By the way, to find out – or to fail to find out – what the initials stand for, go to the EMBO home page; it’s the first and the last information you’re given on the point: “EMBO stands for excellence in the life sciences.” Yes, the true PR touch!)

Remember that the European Directive of 2010 which governs all such studies has, as its “final goal”, the “full replacement of procedures on live animals for scientific and educational purposes”. Why do the people who actually carry out the procedures seem so little aware of this objective that they only qualify their devotion to experimenting on mice to the extent that they can find newer species to try? The explanation is at least partly that the “full replacement” is only to be effected, so the Directive unfortunately stipulates, when “it is scientifically possible to do so”. The date is thus made the scientists’ own property, and they therefore can and do push it steadily into the further distance ahead of them as they move towards Yartsev’s and EMBO’s exciting future. Meanwhile, the rise of such organisations as Understanding Animal Research and its European equivalents, and of in-house PR teams to manage web-sites and other publicity, enables the scientists simply to farm out the ethics and concentrate on their own professional aims.

How strictly professional those aims are becomes disconcertingly clear at the end of the Yartsev article. All that talk of new techniques and new laboratory species, which you might expect to culminate in a vision of world-wide neuroscience-led mental health, turns out, in the last sentence, to be “for the overall benefit of the neuroscience research community”. But then whether the emperor’s clothes were real or not didn’t make any essential difference to his attendant subjects either.

So much for the mouse as viewed, used, and existentially depreciated by practitioners of the life sciences. For the mouse in its true and proper relation to ourselves, I refer you to the Robert Burns poem ‘To a mouse’, which is discussed at the end of the post cited in my first sentence above.

 

Notes and references:

The post ‘Earth born Companions’ can be read here: https://voiceforethicalresearchatoxford.wordpress.com/2017/07/03/earth-born-companions/

The Harwell Institute news is reported in the Guardian newspaper here: https://www.theguardian.com/science/2019/jun/20/uk-mouse-genetics-centre-faces-closure-threatening-research , and the closure of the Sanger Institute breeding programme is announced here: https://www.sanger.ac.uk/news/view/sanger-institute-animal-research-facility-close

The article ‘Social transmission of food safety’ appeared in Science, 7 June 2019.

The ‘emperor’s new wardrobe’ article was published in the issue of Science dated 27 October 2017, and can be read here: https://science.sciencemag.org/content/358/6362/466

EMBO actually stands for European Molecular Biology Organisation. The report cited, with its snappy Americanized title ‘Model organisms: new kids on the block’, can be read here: https://www.embo.org/news/articles/2017/model-organisms-new-kids-on-the-block.

The “final goal” is stated very early in Directive 2010/63/EU, at paragraph 10 of the preamble: see https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=celex%3A32010L0063.

The illustration showing the emperor in his ‘new clothes’, with admiring public, is by Hans Anderson’s contemporary illustrator Vilhelm Pederson.

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