Which Crisis?

The health crisis caused by Covid-19 is unusual in its suddenness and universality, but there is nothing to learn from it about human health. We already knew that humans were liable to such infectious diseases; much of our medical research and development over the last two centuries has been devoted to identifying and disabling the bacteria and viruses that cause them. Research into Covid-19 will differ only in the haste and internationalism which correspond with the irruption of the disease. More important then, because this is something that we haven’t even started to put right, is that Covid-19 is also a crisis in our relations with other animals or, rather, a flagrant symptom of it.

The pathway taken by the virus, from bats to pangolins to humans, has now been more or less confidently identified, and the particular setting for it, the notorious wet markets of Wuhan, have been prohibited together with other such markets in China (see this blog on 28 February). But as the Mirror newspaper reports, “multiple species are still being crammed together, slaughtered and sold, in filthy conditions, contaminated with blood and faeces, at countless markets in other Asian countries.” Live-animals markets even exist in New York, selling less exotic animals perhaps, but with the same crowding, on-site slaughtering, and consequently morally and physically squalid conditions. (Two petitions which you may like to sign on this subject are linked in the notes below.)

But aren’t even conventional slaughterhouses “contaminated with blood and faeces”? At any rate, the more mainstream forms of agriculture are not innocent by-standers in the Covid-19 story. An excellent piece by Laura Spinney in the Guardian (‘Is Factory Farming to Blame for the Coronavirus?’) uncovers their part in creating the conditions for that and other such animal-derived infections. Not just have the huge factory farms pushed the small farmers of Asia out of their traditional lands and into ‘specialist’ wild animal trading, working in the forest and other uncultivated lands where the animals have hitherto been relatively undisturbed. Such farms also create, on their own account, ideal virus-incubating conditions: that is, a target host of unnaturally crowded and unhealthy animals, with none of the genetic variety that can inhibit transmission. These conditions, says Spinney, “can result in the ratcheting up of the virus’s virulence. If it then spills over into humans, we are potentially in trouble.”

Among the products of such agriculture have been campylobacter, Q fever, hepatitis E, and various mutations of the influenza virus. As to this last case, industrial agriculture’s “strategic alliance with influenza” has been fully documented in a recent book by the evolutionary biologist Rob Wallace, whose title bluntly states the case: Big Farms Make Big Flu (Monthly Review Press, 2016).

The more general truth is that farms make diseases. Humans have been fashioning their illnesses out of animals, along with their food, clothes, motive power, amusement, and latterly lab equipment, for millennia. In his comprehensive history of medicine, The Greatest Benefit to Mankind, Roy Porter has to begin (on page 18 of 700) with the agricultural revolution of the neolithic period, because this was where the trouble began. Newly crowded human populations (more humans could now be fed from a given area CoeDeadlyVirusof land) were living off force-crowded animals, and so creating the right conditions for “pathogens once exclusive to animals” to jump across to humans:

Many of the worst human diseases were created by proximity to animals. Cattle provided the pathogen pool with tuberculosis and viral poxes like smallpox. Pigs and ducks gave humans their influenzas, while horses brought rhinoviruses and hence the common cold . . . water polluted with animal faeces also spreads polio, cholera, typhoid, viral hepatitis, whooping cough and diphtheria.  

Smallpox, to take one especially baneful example, was a “ratcheting up” in human hosts of the cowpox virus. Edward Jenner, the man who pioneered the use of cowpox as a prophylactic against it, understood well in the 18th century the context which Porter describes. He stated it thus in his Enquiry into the Causes and Effects of the Cow Pox (1798):

The deviation of man from the state in which he was originally placed by nature seems to have proved to him a prolific source of diseases. From the love of splendour, from the indulgence of luxury, and from his fondness for amusement he has familiarized himself with a great number of animals, which may not originally have been intended for his associates.

As I said, we haven’t started to put this problem right, but of course there’s been plenty of remedial action. Laura Spinney mentions avian flu virus H7N9, first found in humans in 2013; a vaccine was developed against this virus in poultry once it became a serious threat to the economics of chicken farming. Now a similar approach – that is, curing the result and not the cause – is being used against African swine fever, a disease which is not yet known to affect humans but has been killing millions of pigs in China before their profitable time (though it appears to be relatively harmless in the wild animals from which it came). A vaccine against it has been devised which, we’re encouraged to believe by a veterinary epidemiologist (that title itself tells a wretched story), justifies “guarded optimism”, although “more testing of safety and efficacy is needed.” [Science, 20 March]

Yes of course, it always is, and here more than ever, when we see research patching up the pathologies which research largely made possible in the first place, one is reminded of that scientist for all seasons, Dr Grant Swinger, alert to every new fashion and opportunity in big science and to the funds which lubricate it (he was the brilliant invention of the late Daniel Greenberg). Still, we certainly find ourselves in urgent need of Dr Swinger and his fellow-professionals at present, so let’s see how they’re getting on with the scourge of Covid-19.

Animal-research laboratories are of course being affected by the pandemic like any other work-place, except that they can’t simply be closed or even put on reduced hours, because there’s a population of animals to keep alive or not. We’re told that labs in the USA are “currently grappling with the best way to care for the millions of mice, monkeys, and other research animals they care for across the country”. One way to do this, of course, is to put them down – ‘take care of them’ in that sense – and a report in Science’s online news for 23 March does indeed announce that “Labs are euthanizing thousands of mice in response to coronavirus pandemic.”

There is no doubt great reluctance to resort to such measures, and one researcher calls the loss “heartbreaking, scientifically and emotionally”. The distress is surely sincere, but it illustrates the ethical non-sense inherent in animal research. (You may recall a similar cry of distress from farmers who lost cattle in the UK’s foot and mouth outbreak earlier this century.) For by way of mitigating the offence, the director of animal resources at Johns Hopkins University explains that many of these mice “would have been euthanized anyway, because, for example, they weren’t born with the genetic profile the lab needed for particular experiments.” It’s just a case of hurrying things up, of doing “two to three weeks’ worth of culling in the course of a single week”. The director himself is “assisting with much of the culling”. This is a reminder of animals bin 3something which the word “heartbreaking” tends to obscure, that killing animals, whether un-needed or at the end of their living usefulness, is a daily routine in laboratories. “Our top priority is animal welfare”, says another lab director, reporting on this crisis. It’s a very familiar claim, but it’s a pious untruth. A laboratory in which it was true would have to find homes for its animals and then close down.

Fortunately the great supplier to the world of GM mice, the Jackson Laboratory – familiarly ‘Jax’ – at Maine and elsewhere (see this blog on 3 July 2017) is not suffering similar heartbreak. Not only has it “not increased its culling” (the routine toll in the Jax labs must constitute a daily massacre), but the demand for ‘mouse models’ susceptible to Covid-19 has prompted “the Jax team” to undertake “a large-scale in vitro fertilization (IVF) program”, so that “very shortly, there’ll be thousands of these mice available to the scientific community.” Meanwhile, all other specialized mice are fully available. Incidentally, for anxious researchers who may be asking themselves “Can humanized mice (immunodeficient mice engrafted with human CD34+ hematopoietic stem cells) be infected with Coronavirus?”, the Jax FAQs section has a reassuring answer: “the chances . . . is [sic] extremely remote.” Well, that’s always been regarded as safe enough odds in the past.

There has been some suggestion that the present urgency may actually have benefited animals, by allowing researchers to conduct clinical trials of possible vaccines straight after in vitro studies, without the usual animal testing. The safety and effectiveness of this way of doing things will thereby have been clearly established. But is this really happening? As far as I can tell, it has applied only to the ‘repurposing’ of therapies already tested and approved in the conventional way for other conditions: for instance, as the journal Science reports, “drugs that have performed well in animal studies against the other two deadly coronaviruses, which cause SARS and Middle East respiratory syndrome (MERS)”. But in whatever way it’s being managed (and the Jax announcement shows that animals are certainly implicated in large numbers), a lot of hard and hurried work is being done to find a vaccine for Covid-19.

To find a vaccine, but to leave the root cause untouched. And this short-termism is reflected in the imagery which is commonly being used to describe our present plight. “Nous sommes en guerre” said President Macron several times in his eloquent and moving address to the French nation on 16 March. Other politicians have used the same imagery in sundry variations. Scientists too. The editor of Science calls for a grand collective effort on the pattern of the Manhattan Project (which produced the first atom bomb). Sir Paul Nurse, director of the Francis Crick Institute in London, recently likened the co-operative endeavour for the nation’s health to the miscellany of ships which rescued the British army from Dunkirk.

All this is understandable, affecting, apt in its way. But it’s the wrong way, not so much because, as was recently argued in the Atlantic, you don’t win wars by skulking at home as we’re required to do at present, but because the attitude itself is mistaken. If there is an enemy in this case, it is we ourselves in our character as compulsive predators. A virus is no more an enemy than a tiger or a bear is an enemy, though all three can seriously harm us in some circumstances. Certain varieties of virus serve us well, for instance the ‘phages’ which can be used to disable some bacteria; others pursue their life-course (or life-like course, since viruses aren’t a self-sufficient life-form) in ways that are indeed capable, by chance, of killing us. The trick is to keep those, and their natural hosts, at a proper distance.

The situation is well understood in one of the earliest of all myths, the quest of the Babylonian King Gilgamesh to destroy the monster Humbaba in the far-distant Cedar Forest. Humbaba, with his “terrifying roar”, is spoken of and feared by the people as a monster, but he seems to do no pro-active harm at all. Simply being feared from a distance is his job. One translator of the epic, Stephen Mitchell, says “Humbaba has his appointed place in the divine order of things. He has specifically been commissioned to be monstrous by one of the great gods, because humans are not supposed to penetrate into the Cedar Forest and chop down its trees.” Or as Mitchell has Humbaba himself say, “I am the forest’s guardian. Enlil / Put me here to terrify men.” [pp.125, 31] It might be Covid-19 talking.

In so far as Gilgamesh gets wisdom from the disaster which his killing of Humbaba turns out to entail, it consists in returning to his own city, to his own proper sphere of life, and staying there. Something of this ancient lesson we may be able to learn from the present crisis, provided we see what sort of crisis it is: a health crisis just for the moment, but more importantly a long-term moral crisis habitually injuring us in ways like this until we at last put it (that is, put ourselves) right.

 

Notes and references:

Petitions against the live-animal markets of New York and elsewhere can be signed here: https://support.peta.org/page/17791/action/1?utm_source=PETA::E-Mail&utm_medium=Social&utm_campaign=0320::veg::PETA::E-Mail::PE%20URGENT%20Help%20Shut%20Down%20Live-Animal%20Markets%20WHO::::pads  and  https://support.peta.org/page/17888/action/1

The Mirror article, published on 26 March, can be read here: https://www.mirror.co.uk/news/world-news/coronavirus-wet-markets-still-selling-21762902

The Guardian article, published on 28 March) is here: chttps://www.msn.com/en-gb/news/spotlight/is-factory-farming-to-blame-for-coronavirus/ar-BB11Qjbo?li=BBoPWjQ&ocid=mailsignout

Quotation on the agricultural revolution is from p.18 of Roy Porter’s The Greatest Benefit to Mankind: a Medical History of Humanity from Antiquity to the Present, HarperCollins, 1997. Porter’s quotation from Jenner’s book is on p.19.

The Science news story about African swine fever is on p.1285, 20 March (vol.367). The online news about culling populations of lab mice can be read here: https://www.sciencemag.org/news/2020/03/it-s-heartbreaking-labs-are-euthanizing-thousands-mice-response-coronavirus-pandemic. The quotation about re-purposing drugs is from an article about Covid-19 research in the issue for 27 March, ‘Race to find Covid-19 treatments accelerates’, at p.1412. This also is the issue in which the editor makes the comparison with the Manhattan Project.

Announcements about Covid-19 by the Jackson Laboratory are on their web-site at https://www.jax.org/jax-mice-and-services/corona-virus-risk-mitigation. You will notice there Jax’s own plentiful use of the ‘top priority’ trope, an interesting study in itself.

The translation of Gilgamesh by Stephen Mitchell is published by Profile Books, 2004. Quotations are from pp.31 and 125.

The print by Sue Coe was issued in 2007, so that in addition to its strength as activist art it illustrates the perennial nature of the harms we inherit by intruding improperly into the lives of other species. The dead animals notice is from a photograph taken by Brian Gunn of the International Association Against Painful Experiments on Animals.

Earth-born Companions

When Oxford University was first required to estimate its annual usage of animals in research and teaching – this was in 1875 – the tally was about 30 frogs and smaller unspecified numbers of fish, dogs, rabbits, insects. No mice were mentioned. In 2016, the University used 226 frogs but more than 200,000 mice.

I don’t know when mice overtook frogs as the leading victims of animal research. Now, in the U.K. at least and probably everywhere, they account for well over 60% of all experiments and a much higher proportion of the GM breeding programmes. A huge industry and international trade has come into being, devoted to the creation and exchange of genetically altered mice. Two of its primary sites are the Medical Research Council’s establishment at Harwell in the U.K., and the Jackson Laboratory in the U.S.A.

As well as its own research, MRC Harwell supplies mice to other laboratories round the world, either live or as frozen sperm or embryos (see web-site for prices). In more detail, its services include (just to give an idea of the sort of thing) “Production of blastocysts and pseudo-pregnant females [a blastocyst is a cluster of cells in the very early stage of embryo development]… Uterine transfer of injected blastocysts to pseudo-pregnant foster-mothers [the foster-mother is the female into whom the foetuses extracted from the first mother are inserted. Neither mother survives the process] … Oviduct transfer of injected embryos to pseudo-pregnant foster mothers … Harvest and preparation of F0 transgenic embryos …”, and so on. The gruesome gynaecology of all this, I won’t attempt to describe: a sample guide to one of the procedures, with illustrations, is referenced below. MRC Harwell bred over 213,000 mice in 2016, but this number would not include the mice archived or traded in unborn condition, or the wastage in mothers and unviable offspring.

The Jackson Laboratory, based in Bar Harbor, Maine, does things on an even larger scale. Like Harwell, it does its own research work. In addition, more than 3 million ‘Jax’ mice, from a selection of over 7000 genetically defined varieties, are sent out to other institutions.

A brief digression now on the likely experiences of these Jax mice at their destinations. Since the Jackson Laboratory receives state funding, it has to conform to national guidance as to the care of its own animals. The same does not apply to the privately funded or commercial laboratories in the U.S.A., well over 800 of them, to which Jax mice may be sent (still less, of course, to laboratories in other countries). These establishments are regulated only by the Animal Welfare Act, whose definition of ‘animal’ does not include mice (or rats or birds). This glaring anomaly is genially described as a “quirk” by the National Academy of Sciences, but actually it was a very deliberate omission, and one which was later emphatically fixed into law by the so-called ‘Helms Amendment’ of 2002. Senator Jesse Helms pointed out to his fellow-senators during the debate that a mouse was much better off in a laboratory than being eaten by a python in the wild, and evidently they accepted this as a useful bench-mark for mouse-welfare. Certainly the research industry did; indeed it had sponsored Helms’s intervention. This is just one instance of a consistent historical record. In spite of all the claims in their publicity to be making animal welfare their special concern, research institutions and their agencies have always resisted statutory controls. If they’d had their way, laboratory animals would even now be relying for their welfare wholly on the haphazard kindness of their vivisectors.

Back to the Jackson Laboratory, and the man who founded it in the 1920s, Clarence Little. In later years he declared that his institution “has done for the mouse in science what Disney has done for it in amusement.” In fact he hoped that Walt Disney’s version of the mouse might be employed to publicize medical research of the Jackson sort – rather Mickey_-_House_of_Mouseas comic pigs advertise bacon. And certainly Micky Mouse would very expressively have represented what has happened to the mouse since it got caught up in medical research. The Disney studio ruthlessly stylized Mickey Mouse, both to make repeat drawing easier, and to make him highly visible and recognisable (the strange white gloves and bulbous shoes, for instance): this is the mouse subdued to human idea and human use. So exactly is the Jax mouse, standardized as it is, and infinitely repeatable in its 7000 varieties. And just as Mickey Mouse became the iconic cartoon animal, so the Jax mouse established its species as the essential laboratory animal.

Both of these institutions, MRC Harwell and the Jackson Laboratory, belong to the International Mouse Phenotyping Consortium, a collaboration whose aim is “to catalogue the functions of the roughly 20,000 genes that mice and humans share”. Last year the IMPC “released an analysis of the phenotypes of the first 1,751 new lines of unique “knockout mice” (mice in whom one gene has been deleted), with much more to come in the months ahead.” The National Institutes of Health, reporting this achievement, was especially interested in the genes which seem to have proven crucial to live birth in the mice. The heading to its announcement optimistically generalized the findings thus: ‘Of Mice and Men: Study Pinpoints Genes Essential for Life’.

Can mouse genetics really translate so usefully into knowledge about humans? In one of this month’s issues of the journal Science, there’s a report of research into “the nature of genetic predisposition to pain”, which is said to promise “new treatments of conditions affecting tens of millions of people worldwide”. Naturally the research used mice, designed and generated for the study (though using at least some Jax mice as starters). But other research in that same area of biology – incidentally an especially malignant one for laboratory animals, with its array of ingenious pain-supplying devices – has questioned the value of mice as models for humans, even where the same genes seem to be involved. An article about it in Yale Scientific said that “there was almost no correlation between human and murine reactions to any of the experimental conditions. For example, if humans were likely to activate a certain gene following trauma, mice were almost equally as likely to activate it or suppress it.” Acknowledging that “mice models are a cornerstone of biomedical research”, the Yale article suggests that this reported research “raises the question of how similar humans and mice really are. With such different genetic responses, perhaps the biology of mice is not an accurate representation of that of humans.”

Bad news in Bar Harbor and Harwell, then, but wait! A professor interviewed for the same article points out that the study only used the one mouse variety, C57BL/6, commonly called ‘Black 6’: “until other mouse strains are studied, the authors need to be cautious in their interpretations that use of mice is irrelevant to human responses.” Get out those order books, then, and let business resume.

The Yale article was headed ‘Of Mice and Men: The Mouse as a Model for Human Disease’. The upbeat NIH piece, you’ll recall, was headed ‘Of Mice and Men: Study Pinpoints Genes … etc.’ But it’s not much of a coincidence: that phrase, with its neat alliteration and reassuring link with a vaguely remembered literary classic, has also caught the imagination of many other science writers on this subject, or has at least appealed to them as likely to catch the imagination of their readers. After all, in a poll recently organised by an educational publisher, John Steinbeck’s fine novel Of Mice and Men has been ranked fourth in the “top 100 titles for the American literature classroom … chosen by American literature teachers across the country.” (But then The Great Gatsby came top!) And perhaps, although mice are only incidentally present in it, this story of two displaced and status-less labourers in forlorn search of a home is no bad fable for the modern animal.

But in fact the novel’s title is not the origin of the phrase. Steinbeck himself was borrowing it in his turn from the poem ‘To a mouse’ by Robert Burns, first published in 1786. And this certainly is an encounter of mouse and man to set beside and re-appraise the modern Disneyfied mass-mouse and the people who convert it into science.

The poem’s sub-title is ‘on turning her up in her nest with the plough’, for Burns was a farmer when he wrote the poem; he knew the situation. He was, besides, as the poem 220px-PG_1063Burns_Naysmithmakes poignantly clear, unhappy in his own ways, remorseful about the past and fearful as to the future. Accordingly there’s absolutely nothing suggestive of species-superiority in the way he speaks to the mouse, as he contemplates the ruin of her nest. He sees in detail and feels the catastrophe which the mouse has suffered, and he understands suffering as a universal burden, indifferent to species and size. Hence that phrase:

The best-laid schemes o’ mice an’ men
Gang aft agley,       

An’ lea’e us nought but grief an’ pain,
For promised joy!

The poem recognizes the encounter as an aspect of the power-relation whose characteristic modern manifestation we’ve been viewing in earlier paragraphs:

I’m truly sorry man’s dominion,
Has broken nature’s social union,
An’ justifies that ill opinion,
Which makes thee startle
At me, thy poor, earth-born companion
An’ fellow-mortal!

So the spoiling of the mouse’s nest is an incident in a much larger wreckage of that commonalty which Burns beautifully dignifies as “nature’s social union”. But in his poem he reasserts the union, at least between these two now present, pledging a true existential comradeship in those phrases “thy poor, earth-born companion / An’ fellow-mortal”.

And of course exactly this is “how similar humans and mice really are” (the phrase from the Yale article). They really are earth-born fellow-mortals, each in their own sphere liable to “grief an’ pain”. Unfortunately we’ve repudiated that fellowship for which Burns’s poem is a permanent model and recommendation, and have chosen instead to privilege human grief and pain, and to make of the mouse a multitudinous enslaved resource in our ruthless struggles to escape them.

 

 

Notes and references:

The numbers from 1875 were published by the Cardwell Commission in Report of the Royal Commission on the Practice of Subjecting Live Animals to Experiments for Scientific Purposes, HMSO, 1876, Appendix III.

Information and quotation about the work at Harwell appears on its web-site at https://www.har.mrc.ac.uk/

A clear, though highly technical, illustrated account of how a standard procedure works can be found in the article ‘Pronuclear Injection for the Production of Transgenic Mice’ at http://www.nature.com/nprot/journal/v2/n5/full/nprot.2007.145.html

About the welfare provisions in the U.S.A.: the “quirk” reference is from https://www.nap.edu/read/10733/chapter/11; the account of Helms’s amendment is from a contemporary news report in U.S.A. Today, readable at http://usatoday30.usatoday.com/news/nation/2002/05/07/animal-welfare.htm

What Clarence Little said about Mickey Mouse is quoted by Karen Rayder in Making Mice: Standardizing Animals for American Biomedical Research, 1900-1955, Princeton University Press, 2004, p.5

The announcement about the work of the IMPC is on a blog run by the National Institutes of Health at https://directorsblog.nih.gov/2016/09/20/of-mice-and-men-study-pinpoints-genes-essential-for-life/

The article in Science is from 16 June 2017, pp.1124-5 and 1168-71, quotations from pp.1124-5. The Yale Scientific article is from 5 April 2013, and can be read at http://www.yalescientific.org/2013/04/of-mice-and-men-the-mouse-as-a-model-for-human-disease/

The poll of American novels was organised by Perfection Learning, and is reported on their web-site at https://www.perfectionlearning.com/top-100-american-literature-titles.

The picture of Mickey Mouse is from the TV series Disney’s House of Mouse (2001-3). The portrait of Robert Burns in 1787 is by Alexander Naysmith, and is held in the collection of the Scottish National Portrait Gallery.

In the U.K., Animal Aid has recently started a campaign to raise awareness of the mouse, its qualities in nature, and its sufferings in laboratories: see https://www.animalaid.org.uk/animal-aid-new-campaign-mice-matter/