Raising Welfare for Lab Rodents
The science of animal welfare is exploding, offering new ways to improve conditions for millions of research animals a year.
Xander Balwit offers concrete proposals for raising the welfare of animals used in biomedical research for our final article in Issue 03. We’ll be on a brief hiatus for the next few weeks as we prepare for the next Issue! If you’d like to write for us, send a pitch to editors@asimov.com.
A hairless and obese rat grimaced at me from behind the glass—its taxidermied gaze fixed on something across the room. Next to it sat a jar, this one containing a rat bred to prefer alcohol over water. “You can tell that the scientists studying these animals were middle-aged males,” jokes Rich Pell, curator of the Center for PostNatural History. “Male anxieties are written all over them.”
Looking at the bald, heavyset, and immoderate rodents, I saw what he meant. As I continued through the museum—which documents the intentional modification of life by humans—I recalled what the writer Hugh Raffles once said about how research animals “not only bear the burdens of our dreams of health and longevity but also assume the task of living out our nightmares.”
With bloodshot eyes rimmed by inflamed pink lids, this alcoholic rat was nightmarish indeed. These rats, known as AA or P-lines, serve as animal models of alcoholism, exhibiting high alcohol-seeking behavior, withdrawal symptoms, and a predisposition to co-abuse ethanol and nicotine. Of course, AA and P-line rats are not the only research animals bred for the study of disease. The most famous of these is the Oncomouse, engineered in 1984 for the express purpose of developing tumors so that researchers could study cancer in living organisms, rather than in petri dishes. The body of the Oncomouse is visibly covered in lumps—a living template of malignancies.
Across the U.S. and E.U., somewhere on the order of 50 million rodents (~95 percent of which are mice or rats) are used yearly in biomedical research. With a little encouragement, these animals develop preconditions towards cancer, Huntington's, Rheumatoid arthritis, Parkinson’s, sleep and memory disorders, addiction, and more. They are bred, incised, injected, and deprived. By doing so, researchers study pain, genetic disorders, the effect of drugs, and disease pathways in mammals that, while genetically similar to us, are not human beings.1
Their not being human is critical here—as there exists a massive double standard when it comes to protocols for human and animal experimentation. There is an enormously high bar for morally permissible human subjects research, but when it comes to animals, the bar is much lower.2 This is understandable given how much we value human life, but solutions to this disparity are not zero-sum: we can also do better for animals.
In fact, the science of animal welfare is exploding. In 1980, the words “animal welfare” appeared in just nine studies whereas in 2023, that number burgeoned to 1,623. In 1959, the year that British scientists William Russell and Rex Burch introduced the canonical 3R—reduce, refine, and replace—principles aimed at improving the welfare of research animals, not a single published paper mentioned the phrase.
Only in the last several decades have we arrived at an improved understanding of animals’ capacity for welfare—that is, the range of possible positive and negative states an animal can realize over time. This lag may not come as too much of a surprise given that it took until 1987 for people to recognize that human babies feel pain. A startling 77 percent of newborns undergoing blood vessel surgery between 1954 and 1983 went under the knife with only muscle relaxants and intermittent laughing gas. Owing to the general human sympathy for infants over rodents, it follows that it took an additional 40 years for the development of tools such as the Mouse Grimace Scale to establish that rodents could likewise feel pain in measurable ways.
Today, the existence of pain in rodents has been well-established. Temperature preference tests demonstrate that, when given the ability to move freely, rodents prefer to be on temperature plates that neither scald nor freeze them. Other conditional placement preference experiments confirm that rats and mice seek out chambers with pain-relieving drugs after being injured. So, although rodents are incapable of verbally reporting distress, researchers can gauge their pain by measuring biomarkers and proxies such as the way they walk, flinch, or lick their paws.
While the existence of pain in rodents is irrefutable, how it relates to their welfare overall is less clear. After all, the capacity for welfare—even that of humans—is woefully understudied. The non-profit think tank, Rethink Priorities, attempts to calculate this using the equation: capacity for welfare = welfare range × lifespan.
Lifespan is easy to account for, but estimating welfare range is far more complex as it includes measuring empirical traits and relying on certain philosophical assumptions by which to weigh positive and negative emotional states.3 However, pinpoint accuracy here is not the point. These are estimates meant to make it easier to evaluate the cost-effectiveness of various interventions across species. Their value doesn’t lie in their precision but in how they capture our growing understanding of animal experiences, which we can then use to increase animal flourishing even as we continue to use them in our service.
In this spirit, I spoke with a range of experts—from scientists who conduct pain and toxicology experiments in rats to animal ethicists and biotechnologists—about ways to improve the welfare of rodents used in research. Their recommendations fall along a spectrum from behavioral interventions—such as picking up mice in a tube rather than by their tails—to genetic ones, such as breeding animals for better mental health or reduced sensitivity to pathological pain.
Why Use Animals?
It may seem that if researchers are sufficiently concerned about the welfare of lab animals, the best thing to do would be to stop using animals altogether. However, a multitude of factors—from institutional inertia to a global animal-testing industry worth billions of dollars—make this outcome unlikely. Still, there are many who not only push back on animal research for its ethical implications, but for its ability to produce findings that translate into clear human benefit. It is often cited that upwards of 90 percent of biomedical research done on mice doesn’t—for every 5,000 drug compounds tested in mice, only five move into human studies.4
While this statistic surprised and disheartened me, it brought forth a range of responses from those I spoke with. The moral philosopher David DeGrazia remarked that if over 90 percent of research doesn’t transfer to clear biomedical benefit, “It raises a question of whether the money is being well spent and animals are too often harmed with no good coming out of it.” Jeff Mogil, professor of pain studies at McGill University, sees the figure differently. “If we knew what we were doing, it wouldn't be science. It would be engineering,” he says. “So even if less than 10 percent of stuff actually does translate, in my mind, that's amazing.”
Regardless of how one chooses to interpret these numbers, the long history of animal experimentation has brought about undeniably consequential discoveries. As the biotechnologist Alex Telford writes, “Without mouse models, we may never have developed polio and meningitis vaccines, organ transplants, GLP-1 drugs, gene therapies, or any other number of transformative treatments.” So even if translation rates are low, depending on one’s views on how the interests of animals compare to that of human beings, animal experimentation might still seem a net positive for welfare.
Another consideration when it comes to letting the “value” of animal studies determine how much to use them is the question of how much data is needed for reproducibility.
“A lot of the evidence suggests that the big part of the problem is that our sample sizes are just too small and that everything would be a lot more replicable if we used a lot more mice,” says Mogil. “So on the one hand, proponents of the 3Rs want us to use fewer, but the reproducibility people want us to use more.” In other words, more mice could lead to more definitive conclusions, preventing the need for future studies using additional mice to pick up where these experiments, if constrained, would have failed to find statistically significant results. Ironically, those who advocate using fewer mice given that animal experiments don’t replicate may actually be promoting the very conditions that prevent them from replicating in the first place.
Whether the value derived from animal studies justifies their continued use is difficult to resolve. What is clear is that, as long as we pursue animal experimentation, we ought to do all we can not only to improve scientific outcomes but also to ensure the welfare of the animal subjects that enable them.
While general animal cruelty laws go back to the early 1800s, guidelines for the treatment of research animals can be traced back to 1959 when William Russell and Rex Burch proposed a framework for reducing, refining, or replacing animal use in biomedical experimentation. The 3Rs, as they were originally proposed, are:
Replacement: The substitution for conscious living higher animals of insentient material;
Reduction: Reduction in the number of animals used to obtain information of given amount and precision;
Refinement: Any decrease in the severity of inhumane procedures applied to those animals which still have to be used.
Although these principles have improved the standard of care for lab animals, they also contribute to complacency surrounding the question of whether still more can and should be done. In today’s research environment, scientists fill out welfare protocols, and, assured by the existence of the 3Rs, don’t feel they need to go above and beyond their requirements. Nor is this their job. The researchers I spoke with were dedicated scientists—running busy labs or entire academic departments. And while it would be nice if every researcher focused on maximizing the welfare of their research animals, a paradigmatic shift in how we approach lab animal welfare will have to come from broader efforts.
Interventions Outside the Mouse
Researchers have already found means of improving the conditions and treatment of rodents in the lab that we can more broadly implement and optimize. Many basic things—social housing, room to forage and explore, tunnel-handling, and administering pain medication before procedures—reduce anxiety and/or pain responses and increase positive behavioral outcomes in rodents (such as an uptick in motivation, play, or exploration behavior).
A 2016 study found that rats who were tickled by their experimenters exhibited Freudensprünge, “joy jumps,” and emitted positive vocalizations.5 While the study focused on the neural correlates of ticklishness rather than ways to increase the well-being of research animals, it revealed that tickling rats suppressed anxious behaviors in a way that supports “Darwin’s idea that ‘the mind must be in a pleasurable condition’ for ticklish laughter.” Put plainly, even something as simple and low-tech as tickling can positively influence the experience of lab rodents.
Another intervention that doesn’t relate to the rodent’s experience, but does help researchers reduce the number of animals used overall is to employ “surplus animals.” At the University of British Columbia, those performing animal experiments must first try to obtain somebody else's surplus rodents, according to Dan Weary, professor and co-founder of the university’s Animal Welfare Program. “These are animals that would be otherwise slated for euthanasia,” he says.6
UBC is a major institution using hundreds of thousands of animals each year, so this policy makes a large difference with respect to the “reduce” principle. In an effort to continue this cycle, researchers at UBC also try to get their animals adopted at the end of their studies. According to Weary, the “recognition that the animal is an individual that has a life beyond this particular trial” positively influences their treatment at the hands of researchers.
Another part of providing research animals with a good life is granting them a good death. For the millions of rodents killed annually in the name of science, their deaths ought to be as painless as possible.
The most frequent way of killing rats and mice is suffocation by CO2. This is done by slowly filling a rodent’s cage with gas, which causes the formation of carbonic acid on their mucous membranes, ultimately leading to respiratory failure. While CO2 has mild anesthetic properties, it is a powerful anxiogenic at lower concentrations—producing feelings of anxiety and fear to varying degrees among rats and mice.
Using other gases alongside CO2 could make the end-of-life experience less aversive to rodents. One example is isoflurane, which is inexpensive and commonly available in laboratories. Isoflurane is an anesthetic that depresses the central nervous system, leading to loss of consciousness and sensation. This could easily be given to animals to render them unconscious before CO2 is administered.
Costing only $0.10/mL, the minuscule amount of isoflurane required to anesthetize a rodent would add only a few cents to the costs of research protocols. It is not an ideal solution, says Weary, “but it's better than CO2” alone. While isoflurane is already administered in some mouse labs, making it standard practice would essentially eliminate the anxiety that accompanies their last moments.
If dispatching animals in the most humane way possible is an integral part of welfare, so too is choosing how many animals to dispatch in the first place. John Streicher, a pain researcher and professor of pharmacology who runs a busy lab at the College of Medicine Tucson says that, while he has had to amend his research protocols in numerous ways over the decades, he has “never gotten serious requests to reduce animal numbers.”
Requests to use fewer animals would issue from Institutional Animal Care and Use Committees (IACUCs), which, at U.S. research universities, are responsible for the oversight and management of animal studies. The composition of IACUCs vary, but they are usually made up of a Chairman, at least one doctor of veterinary medicine, one practicing scientist experienced in research with animals, one member from a nonscientific area, and one member who is not affiliated with the institution other than as part of the IACUC—often a retiree or community member.
The problem with such committees, according to welfare experts like DeGrazia and Weary, is that their composition tends to encourage strong biases in favor of proceeding with studies. Universities are incentivized to produce research, the scientifically trained are socialized into thinking that animals are a necessary part of that research, and members of the public may not have any particular knowledge about animals or possess a large degree of sympathy towards them. So while the non-affiliated member is, in theory, there to represent the general community's interests and ensure transparency—it still seems to Weary that “almost all the decisions that we make about the animals we use, we do in isolation.”
One way that this dispassionate review system could be improved, Weary suggests, is to find a way of making the animals present to the committee—maybe even by having a live rodent in the room. While this may not move the members who are used to working with them, those without such experience might feel affected by the presence of an animal during their deliberations.
Perhaps, a demonstration of the procedure that will be done to the animals could also encourage committee members to think more about the animals’ interests. Regardless, mandating that these boards have an animal representative—such as the animal itself or an animal ethicist—could help raise the bar for harm-benefit analyses.
Interventions Inside the Mouse
Genes are fundamental to the welfare of an animal. Despite making refinements to an animal’s environment or handling, if their genes confer traits that lead to misery, welfare improvements can only go so far. Genetics govern pain sensitivity, determine disease susceptibility, affect behavior, and so much more.
Genetic interventions are especially salient when confronting biomedicine’s preferred experimental rodent. Out of the millions of mice used in experiments, one variety, the C57BL/6 or “black-6” accounts for roughly five-sixths of them. This mouse, which has become the dominant research mammal across labs largely by accident, is not known for its robustness. In fact, its well-being is so poor that welfare-inclined researchers would do well to use other lines.
The black-6 mouse has been purposefully inbred to provide researchers with a genetically well-characterized animal model. But unfortunately, it also exhibits the negative effects of inbreeding. The black-6 has a tendency to develop cardiovascular disease, increased sensitivity to cold, hearing loss, and a predilection towards nipping the tails of their cage-mates.
To avoid relying upon animals with these traits, researchers could use mice bred from unrelated individuals to maintain genetic diversity: outbred mice.
“Unless the experiment is specifically about genetics or unless I need a particular knockout strain that's only made on the black-6 background,” says Mogil, “we do all our experiments in outbred mice, such as CD-1s or Swiss Websters.” Typically twice the weight of the black-6, outbred mice are much more robust and can easily engage in species-typical functioning. And because they retain greater genetic variation, outbred mice are better for testing the efficacy of a medical intervention over a diverse population. Not only that, Mogil says, but “they're much cheaper—around $8 instead of $40 per mouse. And if you breed them, you get litters of 16 every time instead of getting litters of four every other time.”7
Researchers could also do more to seek out animal models whose genetics are better suited for certain kinds of research beyond those varieties typically used in the labs. This would not only improve translational research but also limit the need to induce conditions in otherwise healthy animals. For example, the study of reproductive diseases such as endometriosis is bottlenecked by the lack of animal models that accurately replicate complex human diseases. Neither outbred nor black-6 mice make good models for endometriosis, as neither menstruates. Instead, scientists could turn to less frequently used, or “non-model” organisms, like the spiny mouse (Acomys dimidiatus). The spiny mouse not only menstruates but has similar hormonal cycles and uterine anatomy to that of humans, and could therefore serve as an ideal model for female reproductive disease research.
Of course, just knowing there are better non-model organisms to use in studies doesn’t help researchers access them. Despite their occasional use in a variety of experiments, there is no centralized vendor for spiny mice. This would need to exist before they could be readily accessible to labs, as would further work on developing handling protocols for these new experimental subjects.8
Both the use of outbred mice and non-model organisms like spiny mice are examples of researchers turning to animals that already have genetics that contribute to higher welfare, but there are also strategies that bring forth such a genetic predisposition.
Compassionate Breeding
Breeding animals so they are genetically more diverse, healthier, and therefore less likely to suffer is part of a larger strategy that Jacob Shwartz-Lucas, director of the Animal Pain Research Institute (APRI), calls “compassionate breeding.” The underlying idea is that, within a population, individuals with higher tolerance and resilience to pain will naturally appear. By selecting for these genes, we could breed animals that fare better in the laboratory.
In fact, rats and mice selectively bred for less anxiety- and depression-related behaviors have existed for decades. And beyond the lab, examples include bulldogs with less difficulty breathing and chickens with fracture-resistant leg bones.
“The capacity for pain and distress evolved to motivate wild animals to avoid harm," explains Shwartz-Lucas. “A mouse is more likely to survive if it is fearful of predators, but a mouse in a lab does not face these same threats, making high levels of pain and anxiety excessive for most studies. The goal of compassionate breeding, then, is not to wholly eliminate pain but to reduce the most extreme and pathological distress to levels more appropriate to an animal's environment.”
Unfortunately, greater sensitivity to pain and anxiety tends to persist among domestic animals because breeders in various industries have historically prioritized immediately profitable traits, such as genetic standardization in lab mice. Selecting for traits relating to welfare, however, can also be good for returns in that less agitated animals tend to be less aggressive, reducing financial losses from injuries—or, in the research context, reducing the likelihood that sustained stress or pain could confound the results of a study.
And whereas it used to be costly for breeders to select for traits beyond the needs of their industry, the falling costs of advanced genomic selection techniques—breeding using DNA sequence data—make it increasingly fast and feasible.9
So although a cancer research lab is unlikely to opt for a mouse line that does not readily develop the type of cancer they study, it would be in their interest to use a line that, despite developing cancer, suffers less than non-compassionately bred mice.
Gene-Editing for Increased Welfare
Gene editing can target specific welfare-related genes in ways that compassionate breeding cannot, such as by directly modifying DNA to completely delete certain genes or splice in entirely new ones from other species.
Kevin Esvelt, a biologist and the director of the Sculpting Evolution group at MIT, has been interested in genetically modifying lab rodents for several years so they experience less pain. To achieve this, Esvelt’s lab has been looking into knocking out FAAH in mice, a gene that encodes the enzyme fatty acid amide hydrolase (FAAH), which contributes to the body’s pain response.10 The idea is that the knockout essentially sedates the mice while still alerting their bodies to avoid danger. The importance of reducing rather than wholly eliminating pain was evident in Esvelt’s earlier experiments knocking out SCN9A, a gene responsible for indicating most types of pain, but without which the mice could not adequately respond to harm from their environments or one another. By contrast, knocking out FAAH makes the animals retain enough pain-signaling to avoid damage. FAAH knockouts have been around since 2001, and since then, studies have indicated their potential as “a new mechanistic approach to anti-anxiety therapy.”11
Beyond pain reduction, Esvelt cares about engineering animals in “ways that can confer resistance to other pathogens.” This is good for both animal and human welfare in that it would help limit the risk of zoonotic disease transmission and ensure that the rodents themselves are healthier. It follows that Esvelt’s lab aims to couple these traits. “In fact,” he says, “we are going to try and insert virus resistance into the very same locus—or location in the genome—as the FAAH.”
An added benefit of focusing on pathogen resistance is its potential desirability outside of a research context. For example, there is a brisk business in “feeder mice” used as snake food. Because of the losses incurred by the spread of disease—among mice and humans—breeders of feeder mice may prefer disease-resistant feeder mice even if they wouldn’t have otherwise prioritized pain-insensitive mice. This would do an immense amount of good seeing as the feeder rodent industry is actually larger than the total number of rodents used for biomedical research, estimated at between 85 million and 2.1 billion vertebrates a year.
Challenges Facing Genetic Interventions
In agriculture and most other industries, compassionate breeding is likely to be a lighter lift than gene editing. This is due, in part, to perceptions of public safety, and by extension, regulation. While gene editing in tightly controlled labs minimizes the risk of escape and interbreeding with wild populations, feeder mice operations are far less controlled. Compassionate breeding avoids the potential risks associated with the escape of gene-edited animals into the wild. So, whereas a gene-edited feeder mouse or agricultural animal might take years to clear FDA regulations, an animal that has been bred for higher welfare would not.
Another reason to favor breeding has to do with attitudes toward gene editing. Polls indicate that while public opposition to genetically engineered animals lessens when modifications improve human welfare, the practice remains contentious.
Skepticism of genetic interventions even extends beyond the public. Many experts in the animal welfare community share concerns that dulling an animal’s sensitivity to pain lessens its capacity for species-typical functioning and does nothing to prevent the further exploitation of animals in research.12 This is why the Animal Pain Research Institute emphasizes improving the overall health and quality of life for animals. Still, because of widespread agreement on the importance of reducing the most extreme and pathological pain, most experts support leveraging both environmental and genetic approaches to maximize welfare.13
Over time, gene editing could occupy a larger niche within compassionate genetic interventions, but only if scientists and companies can avoid alterations that might inadvertently cause animals more pain and suffering. One day, biotechnology may even offer ways to control levels of pain and suffering in extremely precise ways, such as turning off pain neurons just before a surgical procedure.
Until then, however, we ought to focus on what is possible and what people will accept while demonstrating that some of the welfare interventions on offer barely require more effort than what is already being done. After all, animals in biomedical labs have been genetically engineered for decades. So why not edit them in ways that reduce their suffering?
Towards a Welfare Optimum
If one wanted to circumvent the welfare challenges of working with live animals, it could be worth returning to the notion of eschewing their use altogether. By replacing them with various organoid or computer model systems, researchers could avoid producing any negative welfare whatsoever.14
While organoids have proven useful in certain studies, such as testing anticancer drugs on patient-derived cell cultures, they are not feasible for most biomedical research. Streicher, who works on the development of opioid drugs, reminds me: “When it comes to research on pain, we're measuring an integrated behavioral experience that incorporates emotional and affective components. So when I look at my work, I don't think I can replace animals.”
Beyond the affective aspects of Streicher’s research into pain, there is something more fundamentally necessary: immunological response. Organoids and similar systems are incomplete models, which means they lack immune systems—often an essential part of what is being researched in biomedicine as pain and the immune system modulate each other in important ways. So although we can be cautiously optimistic about the value of approaches that mimic tissue-like structures for pre-clinical research, their viability is limited by their simplicity. As complicated biological creatures, we require complicated biological models.
Our relationship with our animal models, then, should be one of deep recognition; the kind felt by Rich Pell when he muses on what he sees reflected in his rats. Animals are the enablers of biomedical research—yet their role is frequently invisible. Why? Are we ashamed? Because if their use really does bolster our science and produce valuable findings, then we ought to understand what they experience in doing so and be willing to defend the claim that we are doing as much as we can to improve their welfare.
Ursula K. LeGuin, in her short story, “The Ones Who Walk Away From Omelas,” posits an ostensibly utopian world that rests on the existence of a single “imbecilic” child tortured in a basement. Everyone in Omelas knows of the existence of the child. They have come to accept that “the profundity of their science” and “the health of their children” rely on this one child’s misery. In Omelas, there is nothing anyone can do for the child. “Those are the terms.”
When it comes to the rats and mice that secure the health of our children and enable our scientific and medical aims, we can do something. So rather than walk away, as the objectors do in Omelas, we can take the actions presently available to us. And in our case, the numbers make it far more compelling to do so. Whereas in Omelas, the “happiness of thousands” rests on the abject misery of one, our situation is multiplied: millions of animals a year suffer in the service of science. Improving their lives through better breeding or handling amounts to an enormous increase in welfare over the long run.
Work towards improving animal welfare is ongoing and certainly not limited to research laboratories. (Although, given how salient the plight of research animals can be to the public and U.S. Congress, the lab is a useful place to focus.)15 As the science of welfare develops, so too will strategies for increasing the well-being of animals used in experimentation. Adopting and developing these strategies, over and above the assurances of existing guidelines, is an essential part of keeping scientific research performed on animals in step with scientific research into their interests.
Xander Balwit is editor-in-chief of Asimov Press.
Thanks to Dan Weary, David DeGrazia, Jeff Mogil, Kevin Esvelt, Milan Cvitkovic, John Streicher, Kathy High, Jeff Sebo, Lynne Sneddon, Jacob Shwartz-Lucas, and Alex Araki for sharing their time and insight with me for this essay. I also want to extend a special thanks to Rich Pell for showing me around the Center for PostNatural History, Jacob Shwartz-Lucas, Alexandr Shchelov, and their colleagues at APRI for providing substantive feedback on early drafts, and Niko McCarty, Antony Kellermann, and Devon Balwit for additional editing support. Lastly, I want to acknowledge Bubba Shwee Shwee and Nutmeg, my pet rats from childhood, whose capacity for curiosity, playfulness, and affection is shared by the animals used in biomedical experimentation, reminding me that a roll of the dice determines how fully any of us get to express our capabilities.
Cite: Xander Balwit. “Raising Lab Animal Welfare” Asimov Press (2024). DOI: https://doi.org/10.62211/81pu-94vt
99 percent of human genes have a counterpart in mice, and the protein-coding genes we share are 85 percent sequence-identical, which puts mice somewhere between primates and pigs in terms of genetic similarity with humans.
Typically, receiving approval from an Institutional Animal Care and Use Committee (IACUC) or an equivalent body is enough. These committees have welfare guidelines in place, but they fundamentally rely on harm-benefit analyses in which humans come out on top.
Rethink has made welfare calculations for 11 species, but rodents are not among them. However, when considering that mice are somewhere between primates and pigs in terms of genetic similarity to us, we can assume that Rethink’s findings for pigs may be transferable to rodents while adjusting for their shorter lifespans.
The reason(s) that so few mouse studies fail to replicate is hotly debated. Speculation is wide-ranging and even amusing. This article contains a non-exhaustive list of reasons that have been cited, including everything from accidentally mixing up mice strains to the microbiome of individual mice.
Kathy High, a bioartist that I spoke with, ran a project from 2009-2019 called “Rat Laughter” wherein she recorded these vocalizations and played them back to lab rats. She said that “they seemed into it,” which, though subjective, was confirmed by an accompanying animal behaviorist. While playing “musical soundscapes” may seem too whimsical to adopt as standard scientific practice, it shows how modest effort and a little creativity could increase welfare accommodations.
Not all research on animals requires they be culled to obtain results. For example, animals used in behavioral studies have nothing physiologically wrong with them which might confound their use in further research.
Inbreeding causes problems when harmful genes are homozygous—that is, passed on by both parents. With non-inbred mice, the frequency of productive matings is close to 100 percent, the age of first mating can be as early as five weeks, and litters can have as many as 16 pups.
It isn’t just a lack of vendors that make working with non-model organisms challenging, but also a lack of antibodies, fully annotated sequences, and transgenics. “There needs to be more tools to lower the barrier of entry into non-model organisms, like Cultivarium but for mammals” says biotechnologist Alex Araki.
Nor is breeding necessarily slow. In 1959, before DNA sequencing, temperamentally-wild foxes used in the fur trade were bred for tameness. In just 6 years (6 generations) a set of offspring began wagging their tails and licking researchers. Even earlier, their stress hormones began dropping and their adrenal glands started shrinking. Lab rodents, with their shorter reproductive cycles and fully sequenced genomes, could enjoy improvements in welfare traits even faster.
The FAAH gene is also present in humans, and a FAAH-FAAH-OUT mutation is thought to be the reason that a 76 year old Scottish woman, named Jo Cameron, experiences no pain or psychological suffering. Cameron’s condition is informing the mission of The Far Out Initiative, an organization focused on developing technological solutions to the problem of involuntary suffering in human and non-human animals.
This was highlighted in a conference APRI organized at the University of Oxford in February to discuss potential scientific and ethical safeguards on genetic interventions to improve welfare.
Nor should improvements in one category lead to laxities in others. Shwartz-Lucas notes that another survey indicates the animal welfare community and laboratory research scientists would not be accepting of reducing environmental aspects of welfare. Giving piglets pain meds is not an excuse to inflict more bodily damage; neither should genetic reductions in pain be an excusable reason to treat animals worse.
It is worth noting that some philosophers and researchers have raised concern that organoids might become capable of supporting consciousness and so merit some welfare consideration as well.
It is worth mentioning that more than 100 billion animals are killed for meat and other animal products every year. So while I’ve focused on research animals here, which number in the millions, welfare improvements directed at farmed animals make an even larger dent in overall welfare.
That's a great read, especially for a large audience.
As I'm quite involved in this field, I found this article to be an honest view of the current situation.
I might gain some insight by developing the actual efforts of the scientific community in homecage monitoring and automation. A lot of efforts are ongoing in this field and will positively affect the welfare of these animals.
In addition, open data with FAIR principles should be considered the next major effort in preclinical studies. The publication strategy emphasizes data analysis and hypothesis testing as the main outcomes of science. However, the underlying data is often hard to find, poorly documented, and not accessible for automation in many cases.
BioFAIR (https://biofair.uk) seems to be moving in the right direction, as recently announced. Hopefully, national stakeholders will see the benefits of this kind of project.
Xander, really enjoyed this piece! Probably one of the most interesting, balanced and well researched articles I've read.
There are a few additions that could be made to your suggestions on welfare improvement. First is better monitoring and a better consistency/standard of day-to-day care.
Currently, in facilities that house 10k-100k animals, a human needs to check each cage once a day, and also do any basic care operations (food/water/bedding exchange, removal of fighting animals) by hand. As you can imagine, even in best-intentioned facilities, this is not 100% - simply because of constrictions on work-force. E.g. when it's Christmas or COVID season suddenly you may have half a capacity.
Second is better reproducibility of data collection. Right now, the level of tech in animal research is that almost everything is measured by physical human hand. I.e. - want to know how strong a mouse is? Have it grab a force sensor and pull it by its tail. Then repeat 10x to get a reasonable average. Because the tech is so poor, human factor is high, so reproducibility is poor. Also, manual handling causes stress, another source of lost welfare and reproducibility.
For anyone not working directly with animals, these two issues are almost always unknown.
I finished my PhD at Harvard about a year ago, engineering gene therapies for aging. To measure the effect of these therapies, I had to do all the above - and it took me about 8 months of continuous work to perform the manual health assays necessary to get a basic dataset.
It was in fact so bad that I realized that 1) getting data from animals was a civilization-scale bottleneck 2) the equivalent of "phenomics" for health had never been created, by anyone.
So I quit academia to build a company around this (Olden labs) - with my answer to the above is to engineer automation that vastly improve data collection, monitoring and basic care.
I'd argue that if we can deploy these at scale and get to a world where animals are routinely monitored 24/7 with objective metrics and alerts, we can also quantify welfare much better - and therefore design and test welfare interventions like the ones you proposed above.
On which note - I do have to say I'm skeptical about engineering away pain. People without pain sensitivity have short lifespans and are always bruised. It's there for a reason. And academics don't want to use models that have different/compromised behaviors from the getgo.