Mus Homunculus in the USA

The variety of mouse commonly used in scientific research is Mus musculus, meaning ‘mouse (little mouse)’. A more accurate name would be Mus homunculus, ‘mouse (little man)’, since this has become the preferred model or manikin for almost every aspect of the human condition supposed capable of study in laboratories. The American journal Science, a peer-review publication which also reports on research published elsewhere, shows the mouse ceaselessly passing by in all its myriad human substitutions: to take this past month alone, Mus homunculusMouse in Bosch 'Garden' has been modelling fungal infections, cancers of all kinds, effects of gender on immune responses, Alzheimer’s disease, the role of glutamine in aging, neuro-developmental disorders, obesity, botulism, progeria, dengue fever, and even empathy (that well-known human virtue).

In the USA the numbers of mice being used in these ways cannot be known, since no systematic count is published or even kept. The Animal Welfare Act, which has supervised lab animals (among others) since 1966, amended its “definition of animal” in 2002 expressly to exclude “birds, rats of the genus Rattus, and mice of the genus Mus, bred for use in research”. Some external oversight of the management of these animals there is, when federal funds are involved in the research, or if the laboratory in question has volunteered to be on the lists of the Association for Assessment and Accreditation of Laboratory Animal Care. This latter organisation may even count the rodents used in its accredited laboratories, but it keeps the numbers confidential, and they’re not collected into any national total. Nor is there any national record of the severity of experiments using the excepted animals.

Incidentally, one common method of counting the mice used at any particular laboratory, should a number be required, is to count the cages, and then to apply some sort of occupancy or turnover rate (for which there’s no generally agreed formula) in order to produce a yearly total. This hit-and-miss method pathetically reflects the existential flimsiness of the American mouse, defined by its transience.

That practitioners favour the present state of more or less ignorance is sufficiently evidenced by their National Association for Biomedical Research (NABR), which vigorously lobbied for it when the 2002 amendment was under discussion, and which continues to defend it. Accordingly, there has been some surprise and indignation on their part at the publication this month of a paper, written by a former laboratory vet, that offers a reasoned estimate of the numbers they did in fact get through in 2017-18. The objections have been partly to the idea of advertising the numbers at all: a “narrow, decontextualized focus on counting animals”, says Speaking of Research, another advocacy grouping, “is a disservice to thoughtful consideration of animal welfare, science, and public health.” But the count itself has also been disputed (why is this somehow familiar?). Speaking of Research makes its own estimate, appropriately un-narrow: “11-23 million” (these are numbers for all animals, so deduct about 0.75 million to get at the excepted ones). That illustrates at least the level of uncertainty on the subject, since this is an organisation of professionals with easy access to whatever information there is. The NABR puts the number at “just under 15 million”, convincingly precise, but no evidence is provided to support it.

The author of the paper that has caused this controversy, Dr Larry Carbone, believes the true number to be very much greater. He has aimed at something more serious than what Americans call a ball-park figure, such as the others are evidently content with; he has worked it out and shown his working. Collecting his information from a sample of laboratories, either by direct questioning or by means of Freedom of Information requests, he has used it to establish a standard or at least common relation between the number of animals reported as required under the Animal Welfare Act, and the number of rodents used in the same places. For the sake of clarity, Carbone refers to the former as ‘animals’, in inverted commas, highlighting the absurdity of the AWA’s counter-scientific definition. The rats and mice, he calculates, have normally comprised about 99.3% of the total. The national figure for reportable ‘animals’ in 2017-18 was 780,070. Applying that percentage, he concludes that the number of rats and mice consumed in the USA’s laboratories in that year was 111.5 million.

Of this astonishing quantity of mice and rats, Carbone estimates that 44 million were used in “painful or distressful experiments”: that is, in experiments which the United States Department of Agriculture, responsible for administering the AWA, would put in its class D (“with pain, with drugs” or ‘WPWD’) or class E (“with pain, no drugs” or ‘WPND’). Classes D and E correspond more or less to ‘moderate’ and ‘severe’ in UK terminology. As you’ll notice, however, the USDA classification doesn’t assess the pain or distress itself; it treats that as a simple yes or no matter, and then classifies according to whether anaesthetics or analgesics have been used, something which may have to do with the animal’s pain but may also reflect the requirements of the experiment. It’s not a very informative arrangement.

And that’s the first good reason for regarding Carbone’s “focus on counting animals” as indeed a service to “thoughtful consideration of animal welfare”. This veterinary surgeon with years of experience in the research laboratory summarizes it thus:

Rodents’ capacity to experience significant pain and distress in experiments is no longer contested. With over 100 million of these sentient animals born per year for American science, it is time to revisit the adequacy of their welfare protections.

Another good reason is that a calculation like Dr Carbone’s will in time show whether the use of animals in American science is going up or down. He believes that although the direction for the AWA’s ‘animals’is gradually downwards, the rodent numbers are “likely increasing”. Of course the two areMouse image from space research closely connected. The special protections given by law to ‘animals’ make the unprotected species  commensurately attractive to researchers, as allowing a freer hand. For as the Animal Welfare Institute (based in Washington D.C.) says,

Basic standards for their housing and care are not overseen by USDA veterinary inspectors . . . There is no legal mandate to consider alternatives to the use of these animals, or to devise means to alleviate or reduce pain and distress.

But there has been no way of evidencing the increase in their use until now – or until next year, rather. And even if the 111 million number is inaccurate as charged (and let’s hope that, however carefully arrived at, it is indeed an over-estimate), any series of numbers arrived at by a standardized calculation in successive years should provide reliable comparisons.

They would show, for instance, whether the 3Rs principles, notionally accepted by the profession in the USA, are being taken seriously in practice. The NABR refers to them in a conveniently distancing way as a “philosophy” (like Creationism, perhaps, or Swedenborgianism), and at present is urging its membership to lobby against a proposal to establish a National Center for Alternatives to Animals in Research which would promote them. In fact this proposal is one part of a momentous reform bill presently before Congress (and objected to in toto by the NABR): the Humane Research and Testing Act. This most welcome and promising Act would, among other things, “require NIH [National Institutes of Health] to track and disclose all vertebrate animals used, including rats, mice, birds and fish . . . and demonstrate its progress [i.e. in reducing numbers] through bi-annual reports.”

Dr Carbone’s calculation comes, then, at an apt and critical moment. Perhaps laborious detective mathematics such as he has had to use in order to stir up attention to what’s happening in American laboratories will soon be unnecessary, and researchers will be taking proper public responsibility for all the animals – all the vertebrate animals, at least – which they use and destroy in their work.

Notes and references:

The amendment which in just a few words excised birds, rats and mice from the Animal Welfare Act can be seen here: https://www.nal.usda.gov/awic/public-law-107-171-farm-security-and-rural-investment-act-2002

I haven’t tried to cover all the different ways in which the work of a research laboratory in the USA may be overseen as to animal welfare and ethics. For instance, I haven’t mentioned the important Institutional Animal Care and Use Committees, which all institutions that receive federal funds have to appoint, and which do roughly the work that Animal Welfare and Ethical Review Bodies do in the UK (though in a much more permissive environment, made notably more so during the years of the Trump administration).

Speaking of Research’s unfavourable review of Dr Carbone’s paper, including the quoted statement, can be read here: https://speakingofresearch.com/2021/01/12/factcheckneeded-how-are-mice-and-rats-accounted-for-in-the-balance-of-science-medicine-and-animal-welfare/. Its own estimate of numbers, as part of a comparative table of numbers in various countries, is offered here https://speakingofresearch.com/facts/animal-research-statistics/. NABR’s estimate is quoted in a New York Post article (described as a “best guess”, and I assume elicited by the journalist), dated 18 January 2021, here: https://nypost.com/2021/01/18/more-than-100-million-rats-mice-used-in-us-labs-report/

Dr Carbone’s paper ‘Estimating mouse and rat use in American laboratories by extrapolation from Animal Welfare Act-regulated species’ was published in the journal Scientific Reports, 12 January 2021: see  https://www.nature.com/articles/s41598-020-79961-0

 The Animal Welfare Institute is quoted from its good summary of the situation titled ‘Rats, Mice, and Birds’, here: https://awionline.org/content/rats-mice-birds

A brief account of the proposed Humane Research and Testing Act can be read here: https://www.caareusa.org/humane_research_and_testing_act_of_2020_introduced

The first illustration is a detail from the late 15th century painting by Hieronymous Bosch, The Garden of Earthly Delights, in the collection of the Museo del Prado in Madrid. The roundel illustration shows the ‘mission patch’ for Rodent Research-IV, one of many research projects using rodents on the International Space Station. It’s aimed at understanding the effects of prolonged space flight on health, and more largely the processes of aging.

Fun We Had in 2020

Last year was a difficult one for many animal research laboratories (as reported in this blog: see notes below), difficult also for science conferences and other such networking. However, the Concordat on Openness, to which many bio-science institutions subscribe, held its end-of-year awards ceremony and issued its annual report as usual. The ceremony, held online, lacked the familiar prize-day atmosphere, of course, but the report seems as keen and boyish as ever. In fact Covid-19 has had some benefit for the Concordat project of “public engagement”, much of which is an online matter anyway, for as the report says, “One impact of the pandemic has been to increase the perceived relevance of biomedical and health research for the public.”

It’s easily understood. Conversations between grateful patients and the specialists researching their disease have been a common feature of animal research publicity. But now the specialist can address a whole grateful population feeling immediately vulnerable to the disease in question. In fact Understanding Animal Research (UAR), the promotional organisation which runs the Concordat, took early advantage of this “time of national emergency when people are focussed on their health” and commissioned a survey of attitudes to animal research during the first lock-down of 2020. This survey found that 73% of respondents would accept the use even of dogs and monkeys in research towards a Covid vaccine. (The percentage of those accepting their use for medical research in a similar survey two years ago was around 15.) However, since 29% of the same surveyed group (of 1,027 randomized individuals) opposed the use of any species in any research, it’s reasonable to conclude, as UAR admits, that “many people feel conflicted and remain uncomfortable with the idea of animal research.” In fact that percentage of people who object absolutely has changed little over the period of systematic surveys since 2014.

Anyway, the pandemic has meant that something stronger than the ordinary PR term ‘engagement’ was involved during 2020. Accordingly, the key word in the Concordat’s annual report is ‘share’: signatory institutions “share examples of their commonly used species”; they are congratulated for “sharing issues around animal research” or for “sharing stories on this subject”; they have “wonderful web-sites that share their use of animals with the public”. It’s not just a word, either. Three of the four ‘Openness Awards’ for 2020 went to projects which promoted public participation in some version or analogue of animal research.

Edinburgh’s Roslin Institute (the place which gave us Dolly the cloned sheep) had produced a ‘toolkit’ which enables children in school or even at home to carry out experiments using garden worms. The kit is punningly titled ‘Opening a Can of Worms’, because after all this is PR and, besides, animals are fun. But respectful fun, of course, and the judges considered that “this toolkit encouraged sensitivity in working with living animals to study behaviour.” Here, for instance, is the Roslin toolkit’s sensitive account of why it’s important to understand animal behaviour: “Animals give us companionship, help us do work, provide us with food and clothes, and they help us to study diseases and to make new medicines.” It makes you wonder what animals can have found to fill the time with before humans came and put purpose into their lives.

Southampton University likewise won its award for a ‘toolkit’. This one involved creating a mouse from craft materials and devising instructions for its proper care, a rather more appealing scheme, but equally aimed at familiarizing the young to the premise of such care: i.e. the keeping of animals for research. Both of these projects were clearly aimed at children (“Train up a child in the way he should go: and when he is old, he will not depart from it.” Proverbs, 22). The Mary Lyon Centre’s scheme of participation seems at first to be similarly directed. It’s fronted with a trio of cartoon mice (for the Centre’s business is the generating, archiving and trading of GM mice): they stand on their hind legs, one combing its hair (grooming, you see), the others eating and drinking in human style. We’re invited to “Burrow into the secret lives of mice”. But the purpose is actually a practical one: to get citizen-observers to watch and record the behaviour of mice on film. From their data, an algorithm will be created enabling mice to be supervised and assessed automatically while in their home cages. This is in fact a project for mass participation. The cartoons, puns, etc., are just, I suppose, the ordinary dermatitis of PR.

The fourth award went to Reading University for its publicity about using llamas to research therapies against Covid-19. As recorded in this blog, Reading won an award last year for its llama publicity. At that time, the highlight was an invitation to name a baby llama either ‘Boris’ or ‘Jeremy’. It’s wholly characteristic of the essential disposability of PR that there has been no further mention (or none that I can find) of that animal. The centre of attention this year is called – in much the same facetious spirit – Fifi.

Along with 2020’s emphasis on ‘sharing’, there has been the usual battery of more ex cathedra animal research publicity. The examples provided by signatories include presentations at science fairs, community festivals, schools, clinics, and other public events. Within the institutions, and aimed at staff, students, and any other associates, there have been articles in newsletters, express mentions in interviews and recruitment fairs, citations in reports and policy papers, even “public-facing TV screens across campuses”.

This saturation of publicity is aimed at taking the unpleasant surprise out of the subject, and surely it’s an astute policy and must be to some extent successful. Still, certain aspects of animal research continue to seem, even to practitioners, too unpleasant to advertise, and the Concordat report notes once again (for it candidly does note this every year) that many signatories are showing reluctance to provide “information that might show their research or institution in a negative light.” The report advises them that this is bad policy, and reminds them of “the risks of secrecy”.

The difficulty has very recently been illustrated in the case of Bath University, one of the fourteen ‘Leaders in Openness’ chosen as offering examples of openness to the others (there were 122 Concordat signatories in 2020). For some years scientists in Bath’s Department of Pharmacy and Pharmacology have been researching new chemical compounds for use in the treatment of depression. A news story issued by the university itself in 2017, and up-dated in 2019, spoke of “potential new anti-depressant and anti-anxiety treatment with a unique mechanism of action”, whose “promise” was being excitingly confirmed by its “anti-depressant like effects in mice”. The story ends with a reference to the Concordat and Bath’s own commitment to openness on the subject of animals in its research. So yes, it has been open about the involvement of mice, but much less explicit about how they’re being used – that is, in the so-called ‘forced-swim test’.

Forced-swimming_test

This ‘model’ of depression involves putting mice (or, less commonly, rats) into cylinders half-full of water from which they can’t escape, and leaving them to swim or float as they will for a test period of six minutes. The idea is that they swim when they’re feeling optimistic about finding a way out, but they merely float when they aren’t (they don’t sink). A ‘promising’ medication is something that induces the mice to spend a larger portion of the six minutes swimming hopefully. The protocol for this experimental device, first put forward in the journal Nature in 1977, has been fully described and filmed by researchers at the University of Maryland for the Journal of Visualized Experiments. It’s all posted online, so there’s no secrecy about it. Still, it makes unpleasant viewing (despite the curious good humour of the young presenters: “Good luck with your future experiments!” they cheerfully wish us at the end.)

For that reason, no doubt, Bath University seems to have been disconcerted by a complaint about the test from PETA, which included a request to provide material from its own video recordings. The university’s first official ‘Response to People for the Ethical Treatment of Animals’ justified “the research highlighted” without even specifying what it was. After further complaint, it seems that the university must have discussed the matter with UAR and been persuaded to provide a more complete reply, including the requested film clip. There are now, therefore, two ‘fact-sheets’ on the matter offered to public attention: Bath’s own account and, linked from that, a more extended general account, also with illustrative film, provided by UAR.

This is just the sort of defensive flurry that the Concordat report urges its signatories to avoid by arranging for their own material to be “proactively placed in the public domain”. And of course the advantage of being ahead in that way is that the material has a favourable colouring when it first appears; in particular there’s no suggestion of secrecy or embarrassment about it. It’s what the Concordat calls ‘owning the story’. By contrast, the successive responses of Bath University to PETA’s challenge have necessarily seemed defensive and palliative. We’re told, in a video featuring one of the university’s researchers, that those six minutes of struggle or helplessness are “mildly stressful” for the mice (though in fact the procedure is classed by the Home Office’s as having ‘moderate’ not ‘mild’ severity). The pathetic efforts of the mice to escape up the sides of the cylinder are described as “climbing activities”. The intervals of helplessness are called “periods of immobility”, as if a welcome rest is being taken. The inventor of the forced-swim test, R.D. Porsolt, more frankly referred to the immobile phase in 1977 as “a state of despair”.

That’s not a phrase the Concordat managers would recommend these days, I’m sure, but animal research scientists had fewer inhibitions in the 1970s. To publicize the UAR survey in March last year, the organisation’s director, Wendy Jarrett, gave an interview to an online science news service in the course of which she referred to that period as “the bad old days”. She spoke in general with un-strident reasonableness, and claimed that UAR’s aim was (as its name suggests) only to promote understanding of animal research, looking forward to “a time when everyone understands”, not to insist or expect that everyone should “like” it. But by ‘understanding’ she also meant acceptance, and in line with that she quoted the survey in which “some people said ‘just because I accept something doesn’t mean I like it’.” The main thing, then, is to dislike it permissively, or at least quietly. Accordingly, what Wendy Jarrett meant by “the bad old days” of the 1970s was not the uninhibited cruelty and profligacy of the animal research at that time, but the “animal rights extremism”.

That indeed fitted her account of the succeeding decades, which presented the science as a more or less autonomously progressive enterprise: relinquishing the more contentious uses for animals (cosmetics testing, or alcohol research, for instance), commitment to the 3Rs, showing and telling as much as possible to the public. It may be true as a mere narrative, but the plot is missing. What she didn’t make clear was that the explanatory force behind it all has been the dissent. If there hadn’t been active and adversarial ‘dislike’, who can say how little ethical progress would have been made, or what fraction of the UK’s supervising bureaucracy, or of the systematic apparatus of ingratiation such as UAR and its Concordat, would have come into existence? Despite all the tonic publicity now coming out of animal research, it must be remembered that the practitioners do not in fact ‘own’ the subject: it’s in public ownership, and what happens to it will go on depending on how much dislike of it the public feels, and what the public does with that dislike.

Notes and references:

Some of the effects of the pandemic on animal research laboratories were discussed in this blog last April: https://voiceforethicalresearchatoxford.wordpress.com/2020/04/08/which-crisis/

A fuller account of the Concordat and its influence was given in this blog here: https://voiceforethicalresearchatoxford.wordpress.com/2019/12/13/here-come-the-concordat-folk/.  The 2020 report of the Concordat on Openness on Animal Research is online here: https://www.understandinganimalresearch.org.uk/files/8516/0733/9083/Concordat_on_Openness_Annual_Report_2020.pdf,   and the four awards are reported here: https://www.understandinganimalresearch.org.uk/news/communications-media/2020-openness-awards/

PETA’s account of the Bath University affair, dated 1 December, is reported (with a link to a letter of protest) here: https://www.peta.org.uk/blog/bath-university-swim-test/?utm_source=PETA%20UK::E-Mail&utm_medium=E-News&utm_campaign=1220::viv::PETA%20UK::E-Mail::Bath%20Forced%20Swim%20Test%20Blog::::peta%20e-news

An abstract of Porsolt et al’s original paper in Nature putting forward the forced-swim test, and using the phrase “state of despair”, can be seen here: https://www.nature.com/articles/266730a0

Bath University’s initial response to the PETA complaint is posted here: https://www.bath.ac.uk/publications/open-response-to-peta-enquiry/attachments/response-to-peta-19-july.pdf

UAR’s post about the forced-swim test is here: https://www.understandinganimalresearch.org.uk/news/communications-media/factsheet-on-the-forced-swim-test/.  The University of Maryland account and presentation can be viewed here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3353513/