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.