“Calhoun standing above his mice laboratory in 1971”

by Jesse Olszynko-Gryn  /  March 2016

“…The Human Time Bomb”, which first aired in February 1971, also links concerns about high-density housing to animal behaviour. Towards the end of the episode, head doomwatcher Dr Spencer Quist (John Paul) muses that chickens living in batteries do not become docile as expected. On the contrary, they become so aggressive that their beaks have to be cut off “to prevent them tearing each other to pieces.” For the episode’s writer, Doctor Who veteran Louis Marks, it was only a short, logical step from aggressive poultry to antisocial people. The episode concludes with Quist calling for a Royal Commission on the “roots of violence in modern society.” The factory-farmed broiler chicken was, in the early 1970s, as much a novel convenience of modern living as the concrete tower block, and feather pecking and cannibalism were real concerns.

But the most influential example of “pathological togetherness” lifted from the animal kingdom was not a bird. It was a rodent and, in particular, the laboratory experiments performed on rats in the 1960s by ethologist John B. Calhoun at the National Institute of Mental Health in Bethesda, Maryland. Calhoun built a “rat city” in which everything a rat could need was provided, except space. The result was a population explosion followed by pathological overcrowding, then extinction. Well before the rats reached the maximum possible density predicted by Calhoun, however, they began to display a range of “deviant” behaviours: mothers neglected their young; dominant males became unusually aggressive; subordinates withdrew psychologically; others became hypersexual; the living cannibalized the dead. Calhoun’s “rat utopia” became a living hell.

“Calhoun inside with the mice in 1971”

Calhoun published the early results of his experiments in 1962 in the now-classic Scientific American article, “Population Density and Social Pathology”. As historians Edmund Ramsden and Jon Adams have shown, Calhoun’s rats circulated widely as “scientific evidence” of the dangers of urban overcrowding in human society. His concept of the “behavioural sink” chimed with despairing journalistic reports of “sink estates” and “sink schools” in 1970s Britain. In the west London suburb of Shepperton, Ballard’s children kept mice, purchased from a local pet shop. As his daughter Fay vividly recalled at “Inner Space”, a recent symposium on Ballard at the British Library, the mice “multiplied quickly and then started to eat each other.” She could “still see the bitten headless torsos and separated heads lying in the sawdust.” The mice were kept in a glass box in the front room where the family watched TV and ate together, so her father would have seen them too. He also would have known about Calhoun’s experiments – gleaned from his subscription to New Scientist or from the bulging package of research papers he received each week from his close friend, the psychologist and computer scientist Chris Evans. Ballard probably did not watch Doomwatch. He preferred American thrillers and detective serials such as The Man from U.N.C.L.E. and Hawaii Five-O. Nor were Calhoun’s experiments, described in New Scientist in 1973 as among “the most widely quoted since Pavlov’s dogs first heard the dinner bell”, necessarily a direct influence on High-Rise. Tower blocks were in the air and Ballard had plenty of non-fictional human source material to draw on. Nevertheless, the particular resonance of Ballard’s novel with Calhoun’s research is striking. As a leading Cambridge psychiatrist put it in 1978, Ballard’s High-Rise “describes the human equivalent of Calhoun’s rat behavioural sink.”

mouse utopia
“Calhoun in a mouse utopia in 1970, by White House photographer Yoichi Okamoto”

by James Felton / 22 July 2021

“Over the last few hundred years, the human population of Earth has seen an increase, taking us from an estimated one billion in 1804 to seven billion in 2017. Throughout this time, concerns have been raised that our numbers may outgrow our ability to produce food, leading to widespread famine. Some – the Malthusians – even took the view that as resources ran out, the population would “control” itself through mass deaths until a sustainable population was reached. As it happens, advances in farming, changes in farming practices, and new farming technology have given us enough food to feed 10 billion people, and it’s how the food is distributed which has caused mass famines and starvation. As we use our resources and the climate crisis worsens, this could all change – but for now, we have always been able to produce more food than we need, even if we have lacked the will or ability to distribute it to those that need it. But while everyone was worried about a lack of resources, one behavioral researcher in the 1970s sought to answer a different question: what happens to society if all our appetites are catered for, and all our needs are met? The answer – according to his study – was an awful lot of cannibalism shortly followed by an apocalypse.

John B Calhoun set about creating a series of experiments that would essentially cater to every need of rodents, and then track the effect on the population over time. The most infamous of the experiments was named, quite dramatically, Universe 25. In this study, he took four breeding pairs of mice and placed them inside a “utopia”. The environment was designed to eliminate problems that would lead to mortality in the wild. They could access limitless food via 16 food hoppers, accessed via tunnels, which would feed up to 25 mice at a time, as well as water bottles just above. Nesting material was provided. The weather was kept at 68°F (20°C), which for those of you who aren’t mice is the perfect mouse temperature. The mice were chosen for their health, obtained from the National Institutes of Health breeding colony. Extreme precautions were taken to stop any disease from entering the universe. As well as this, no predators were present in the utopia, which sort of stands to reason. It’s not often something is described as a “utopia, but also there were lions there picking us all off one by one”.  The experiment began, and as you’d expect, the mice used the time that would usually be wasted in foraging for food and shelter for having excessive amounts of sexual intercourse. About every 55 days, the population doubled as the mice filled the most desirable space within the pen, where access to the food tunnels was of ease. When the population hit 620, that slowed to doubling around every 145 days, as the mouse society began to hit problems.

“A figure from Calhoun’s 1962 paper, illustrating the behavior of “normal” and “abnormal” mother mice. Image from John B. Calhoun, “Population Density and Social Pathology,” Scientific American 306 (1962): 139-148.”

The mice split off into groups, and those that could not find a role in these groups found themselves with nowhere to go. “In the normal course of events in a natural ecological setting somewhat more young survive to maturity than are necessary to replace their dying or senescent established associates,” Calhoun wrote in 1972. “The excess that find no social niches emigrate.” Here, the “excess” could not emigrate, for there was nowhere else to go. The mice that found themself with no social role to fill – there are only so many head mouse roles, and the utopia was in no need of a Ratatouille-esque chef – became isolated. “Males who failed withdrew physically and psychologically; they became very inactive and aggregated in large pools near the center of the floor of the universe. From this point on they no longer initiated interaction with their established associates, nor did their behavior elicit attack by territorial males,” read the paper. “Even so, they became characterized by many wounds and much scar tissue as a result of attacks by other withdrawn males.”

“Mouse utopia/dystopia, as designed by John B. Calhoun. images from Animal Populations: Nature’s Checks and Balances, 1983.”

The withdrawn males would not respond during attacks, lying there immobile. Later on, they would attack others in the same pattern. The female counterparts of these isolated males withdrew as well. Some mice spent their days preening themselves, shunning mating, and never engaging in fighting. Due to this they had excellent fur coats, and were dubbed, somewhat disconcertingly, the “beautiful ones”. The breakdown of usual mouse behavior wasn’t just limited to the outsiders. The “alpha male” mice became extremely aggressive, attacking others with no motivation or gain for themselves, and regularly raped both males and females. Violent encounters sometimes ended in mouse-on-mouse cannibalism. Despite – or perhaps because – their every need was being catered for, mothers would abandon their young or merely just forget about them entirely, leaving them to fend for themselves. The mother mice also became aggressive towards trespassers to their nests, with males that would normally fill this role banished to other parts of the utopia. This aggression spilled over, and the mothers would regularly kill their young. Infant mortality in some territories of the utopia reached 90 percent.

This was all during the first phase of the downfall of the “utopia”. In the phase Calhoun termed the “second death”, whatever young mice survived the attacks from their mothers and others would grow up around these unusual mouse behaviors. As a result, they never learned usual mice behaviors and many showed little or no interest in mating, preferring to eat and preen themselves, alone. The population peaked at 2,200 – short of the actual 3,000-mouse capacity of the “universe” – and from there came the decline. Many of the mice weren’t interested in breeding and retired to the upper decks of the enclosure, while the others formed into violent gangs below, which would regularly attack and cannibalize other groups as well as their own. The low birth rate and high infant mortality combined with the violence, and soon the entire colony was extinct. During the mousepocalypse, food remained ample, and their every need completely met. Calhoun termed what he saw as the cause of the collapse “behavioral sink”. “For an animal so simple as a mouse, the most complex behaviors involve the interrelated set of courtship, maternal care, territorial defence and hierarchical intragroup and intergroup social organization,” he concluded in his study. “When behaviors related to these functions fail to mature, there is no development of social organization and no reproduction. As in the case of my study reported above, all members of the population will age and eventually die. The species will die out.”

He believed that the mouse experiment may also apply to humans, and warned of a day where – god forbid – all our needs are met. “For an animal so complex as man, there is no logical reason why a comparable sequence of events should not also lead to species extinction. If opportunities for role fulfilment fall far short of the demand by those capable of filling roles, and having expectancies to do so, only violence and disruption of social organization can follow.” At the time, the experiment and conclusion became quite popular, resonating with people’s feelings about overcrowding in urban areas leading to moral decay” (though of course, this ignores so many factors such as poverty and prejudice). However, in recent times, people have questioned whether the experiment could really be applied so simply to humans – and whether it really showed what we believed it did in the first place. The end of the mouse utopia could have arisen “not from density, but from excessive social interaction,” medical historian Edmund Ramsden said in 2008. “Not all of Calhoun’s rats had gone berserk. Those who managed to control space led relatively normal lives.” As well as this, the experiment design has been criticized for creating not an overpopulation problem, but rather a scenario where the more aggressive mice were able to control the territory and isolate everyone else. Much like with food production in the real world, it’s possible that the problem wasn’t of adequate resources, but how those resources are controlled.”

How 1960s Mouse Utopias Led to Grim Predictions for Future of Humanity
by Marissa Fessenden / February 26, 2015

“…After Calhoun wrote about his findings in a 1962 issue of Scientific American, that term caught on in popular culture, according to a paper published in the Journal of Social History. The work tapped into the era’s feeling of dread that crowded urban areas heralded the risk of moral decay — and events like the murder of Kitty Genovese (though it was misreported) only served to intensify the worry. A host of science fiction works — books like Soylent Green, comics like 2000AD — played on Calhoun’s ideas and those of his contemporaries.

The work also inspired the 1971 children’s book Mrs. Frisby and the Rats of NIMH, which was also made into a 1982 film The Secret of NIMH, notes the National Institutes of Health. Now, interpretations of Calhoun’s work has changed. Inglis-Arkell explains that the habitats he created weren’t really overcrowded, but that isolation enabled aggressive mice to stake out territory and isolate the beautiful ones. She writes, “Instead of a population problem, one could argue that Universe 25 had a fair distribution problem.” But we can take comfort in the face that humans are not mice. The NIH Record spoke to medical historian Edmund Ramsden about Calhoun’s work…”

How 1960s Mouse Utopias Led to Grim Predictions for Future of Humanity
by Marissa Fessenden / February 26, 2015

“What does utopia look like for mice? According to a researcher who did most of his work in the 1950s through1970s, it might include limitless food (of course!), multiple levels and secluded little rodent condos. These were all part of John Calhoun’s experiments to study the effects of population density on behavior. But what looked like rat utopias and mouse paradises at first quickly spiraled into out-of-control overcrowding, eventual population collapse and seemingly sinister behavior patterns. The mice were not nice.

For io9, Esther Inglis-Arkell writes about Calhoun’s twenty-fifth habitat and the experiment that followed: “At the peak population, most mice spent every living second in the company of hundreds of other mice. They gathered in the main squares, waiting to be fed and occasionally attacking each other. Few females carried pregnancies to term, and the ones that did seemed to simply forget about their babies. They’d move half their litter away from danger and forget the rest. Sometimes they’d drop and abandon a baby while they were carrying it. The few secluded spaces housed a population Calhoun called, “the beautiful ones.” Generally guarded by one male, the females—and few males—inside the space didn’t breed or fight or do anything but eat and groom and sleep. When the population started declining the beautiful ones were spared from violence and death, but had completely lost touch with social behaviors, including having sex or caring for their young.”

Calhoun’s experiments, which started with rats an outdoor pen and moved on to mice at the National Institute of Mental Health during the early 1960s, were interpreted at the time as evidence of what could happen in an overpopulated world. The unusual behaviors he observed he dubbed “behavioral sinks.” After Calhoun wrote about his findings in a 1962 issue of Scientific American, that term caught on in popular culture, according to a paper published in the Journal of Social History. The work tapped into the era’s feeling of dread that crowded urban areas heralded the risk of moral decay — and events like the murder of Kitty Genovese (though it was misreported) only served to intensify the worry. A host of science fiction works — books like Soylent Green, comics like 2000AD — played on Calhoun’s ideas and those of his contemporaries. The work also inspired the 1971 children’s book Mrs. Frisby and the Rats of NIMH, which was also made into a 1982 film The Secret of NIMH, notes the National Institutes of Health.

Now, interpretations of Calhoun’s work has changed. Inglis-Arkell explains that the habitats he created weren’t really overcrowded, but that isolation enabled aggressive mice to stake out territory and isolate the beautiful ones. She writes, “Instead of a population problem, one could argue that Universe 25 had a fair distribution problem.” But we can take comfort in the face that humans are not mice. The NIH Record spoke to medical historian Edmund Ramsden about Calhoun’s work: “Ultimately, “[r]ats may suffer from crowding; human beings can cope,” Ramdsen says. “Calhoun’s research was seen not only as questionable, but also as dangerous.” Another researcher, Jonathan Freedman, turned to studying actual people — they were just high school and university students, but definitely human. His work suggested a different interpretation. Moral decay could arise “not from density, but from excessive social interaction,” Ramsden says. “Not all of Calhoun’s rats had gone berserk. Those who managed to control space led relatively normal lives.”

CONDITIONS of a MOUSE UTOPIA’s_experiment.html
Rat Dystopias
by @demystifysci   /  Jul 22, 2020

“…This week, we’ll look at another aspect of multicellularity, one that manifests on a community level, rather than the individual level. To do this, we are going to take a closer look at a paper by John B. Calhoun called Population Density and Social Pathology. I want to look at this paper because the experiments within – an extended trial of rodents in confined conditions – seems to offer perspective on the ways in which a multicellular animal – such as a mouse or rat – functions in the context of a greater whole. The mad-scientist experiment thought up by Calhoun allows us to take a step back and consider what one might be able to say about the human condition, and the ways that our environments affect our psychology. Though the parallels are tantalizing, it is important to remember that we can’t draw clear parallels between humans and experiments done with rodents under even the best conditions. Mice are mice, rats are rats, humans are humans. There is also the fact that these studies were never repeated. They were enormously time-consuming, and seem like a unique result of a man who had spent his entire life working on progressively larger behavioral studies. It seems like Calhoun may have been the only person who was capable of carrying out the experiments – and the lack of reproducibility comes down to the fact that no one except for him was interested in babysitting a quarter acre of rats for nearly a year and a half.  Whatever the case, Calhoun did something extraordinary. In a large barn on his property, he built an enclosure capable of housing thousands of rats. He provided food, water, shelter, and the rats to enjoy it. After more than a year, he emerged a man certain about the fact that human society was driving people to the brink of madness.

John B. Calhoun’s interest in animal behavior when Mrs. Laskey of the Tennessee Ornithological Society taught him to band birds. He published his first paper on animal behavior at the age of 15, and then continued his study of animal behavior as a student of ethology, animal behavior, at the University of Virginia. During his summers at the university, he continued his ornithology work with the Alexander Wetmore, assistant secretary of the Smithsonian Institution. During his PhD his attention shifted closer to Earth, when he began his studies of the 24hr rhythms of the Norway rat. Whatever he found in these studies was enough to keep his attention for the rest of his life, trudging ever-deeper into the  complex world of rodent social behavior.

His first foray into large-scale explorations of rodent behavior took place shortly after his appointment to the Rodent Ecology Project at Johns Hopkins University in 1948. Inspired by what he was discovering at the university, he convinced a neighbor to let him borrow a 1/4 acre plot of unused, forested land. On it, he constructed a 10,000 square foot pen that was open to the elements. He stocked it with ample food, water, and material for building shelters, and dubbed it “Rat Utopia” – the kind of place where a rat would never want for anything. He estimated that the enclosure was large enough to house 5,000 rats, but he was unsure of where the population would stabilize, or what phases it would transition through on its way there. To find out, he seeded the pen with five pregnant females and sat back. For 28 months, he tracked the rodent populations in the pen, noting any behavioral and social changes.

During the two years that he monitored his colony, he found some oddities – the number of rats in the population never exceeded 200 – despite his earlier calculations of a 5,000 rat carrying capacity. In addition to the surprisingly low population density, the distribution of the rats through the enclosure wasn’t uniform. Instead, rats would organize themselves into discrete social units with 12-13 members. He reasoned that this was the natural balance point between a functional society and psychological chaos. Any more individuals and the group would be forced to splinter into a smaller group – perhaps a reflection of the limited number of stable social connections each rat is capable of forming. At the end of the experiment, Calhoun was interested in pushing the limits, to see what kinds of changes began to occur as he increased social density – the number of individuals in an enclosure. To this end, he secured a strain of domesticated albino Norwegian rats – the quintessential lab rats – and built an slightly more complex indoor enclosure. This version was significantly smaller than the 1/4 acre pen. It was square, partitioned into four sections, with a pane of glass across the top that allowed the researchers to look into the pen. There was also a door on the side that would allow the researcher access. No photographs of the setup are available, so we will have to rely on the illustrations Calhoun himself made for his Scientific American publication.

“Rat Utopia #1. Pens I and IV are not connected to each other, but are connected to pens II and III, respectively. Topology of the enclosure is linear, with pens II and III serving as the center.”

There are four chambers, separated by an electrified fence, with a staircase connecting three of four chambers – they are the black grids that bridge compartments I & II, II & III, and III & IV. There is no staircase between chambers I and IV, effectively creating a linear flow through the habitat. At the edges of each compartment are what amounts to housing towers, with covered nesting quarters at the top of a spiral staircase. Compartment IV shows a cutaway perspective on the tower, demonstrating the apartment-like setup of five nests on the inside. In each compartment there were food containers and water trays, offered ad libitum.  To initiate the experiment, Calhoun seeded the four compartments with an equal number of male-female pairs and waited for their populations to grow to 80 individuals. After that point, he removed any new pups that were born so the population remained stable at 80 individuals. This amounted to 20 individuals per compartment, which was a 75% increase over the preferred group size of 12 in each compartment. After several months in the pens, he observed that the rats would cluster into a few distinct types of groups – small, medium, and large. The medium groups had equal numbers of male and female rats, but he reliably observed that small groups tend to skew female, while larger groups skewed male. The small groups – i.e. many females to a few males – were found predominantly in the end pens, I and IV, while the larger groups were found predominantly in the center pens, II and III. This meant that the male population was predominantly relegated to those two pens. Overall, the center pens had a much larger population that the end pens. The mechanism by which this gender and population segregation occurred was aided by a synergy between Calhoun’s design and the process by which the rats oriented themselves in the social hierarchy. Young male rats undergo a period of aggressive status determination, during which they fight for dominance. During this period of fighting, many young rats would awaken early to forage for food before the rest of the colony was active – effectively avoiding the incessant fighting while getting read for the day.

“The wire-mesh food hopper used in the experiments that displayed the development of a behavioral sink. Habituation to feeding together at a specific hopper caused a conditioned desire to eat at the same location, in the presence of other rats.”

This early rising behavior prevented fights, but paradoxically led to an increased density of males in the two middle compartments. This was likely due to two factors – food and access. Calhoun had developed a special feeding trough, where kibble was hidden behind a wire mesh, that required animals to spend much more time and effort during feeding. Since pens II and III were accessed from two sides, they quickly accumulated a larger population, where this sort of behavior seemed to amplify itself to the degree that Calhoun reported he rarely, if ever, saw animals eating by themselves. So when male rats in pens I and IV woke up early to go get food, they would go to the main watering holes – pens II and III – to get it. But the dominant males in pen I and IV had set up their living quarters at the bottom of the single ramp that led to those compartments. When these early risers attempted to return, these dominant males would wake and drive them back into the central pen – effectively causing the population density of the central pens to increase, while the peripheral pens lived quite comfortably. This spontaneous increase in population densities in the central pens of the experiment created what Calhoun referred to as a “behavioral sink,” a situation that far surpassed the population densities the wild rats in the first experiment appeared to prefer. This sort of density resulted in severe disruption of normal rhythms, which Calhoun found to be most apparent in the nesting behavior of the females.

“Rooms” are replicates of an entire 16 month experiment, and pens correspond to roman numerals I-IV. The increases in eating took place in one of the central pens each time a specific kind of food hopper was used. In all three cases, population of the central pens is much greater than the edge pens – though this relative concentration is not the same in all trials. Black and hatched bars represent male female ratios, which are not as robust across populations – or as simple as the story reported by Calhoun in his Scientific American piece. In the brood pens, the low population I and IV pens, where there was a high female:male ratio, Calhoun measured a 50% survival rate of newborn pups. This seems low, but rats have large litters, up to 15 pups at a time, because in the wild there is some significant percentage that does not survive to adulthood. However, in the females that were in the high-density feeding pens, II and III, between 85 and 90% of the pups died before weaning.  Calhoun attributed this lower likelihood of survival to the overabundance of males that would relentlessly pursue females, whether or not they were willing to mate. This meant that pregnant females, normally free to occupy themselves with the tasks of nestbuilding, were constantly being interrupted by males looking to copulate. This effectively short-circuited the female nesting behavior and although they were pregnant more frequently,  they were much worse at taking care of their litters.  The behavioral sink had long-term negative effects for females, who died at a much higher rate than the male rats. By the end of 16 months, a quarter of the females had died from complications with pregnancy or birth – while only 15% of males had died from any cause. That is not to say, however, that the males didn’t suffer any negative consequences.  Some males managed to avoid the worst of it, and were permitted to remain in these peripheral pens – but in return, these “phlegmatic males” had to accept the dominance of the sentinel without argument. They would spend most of their time burrowed with the females, rarely engaging in sexual behavior of any kind.

“Powder feeder used in the second round of experiments, where rats did not have to spend a significant amount of time acquiring food. The lack of social conditioning prevented the formation of a runaway behavioral sink.”

They would emerge to eat and sleep, and then return to their sleeping quarters until they were stirred by physiological need. The dominant males that managed to secure brood territories were largely exempt from complication – but in the densely populated middle pens, the fight for dominance never ceased. Periods of relative peace would be interrupted “at regular intervals during the course of their waking hours, [when] the top-ranking males engaged in free-for-alls that culminated in the transfer of dominance from one male to another.” Even those males that succeeded in making it to the top of the hierarchy would periodically go berserk, “attacking females, juveniles and the less active males, and showing a particular predilection -which rats do not normally display – for biting other animals on the tail.” Those males that did manage to rise to the top of the dominance hierarchy displayed other, abnormal behaviors. There were the pansexuals, who would engage in sexual activity with anyone – male, female, juvenile – that would tolerate their advances.

The “somnambulist” rats were the ones that “ignored all the other rats of both sexes, and all the other rats ignored them.” The “probers” were the final group of males that emerged in the densely populated central pens. They were hyperactive, constantly searching for sexual partners. But their coitus was disturbed, as they would submit to vicious attacks from the dominant rats without defending themselves, and would return, over and over again, to their position at the top of the ladders that led to the brooding pens. There they would wait for passing females with whom they could engage in coitus. These probers were incapable of performing ritual mating practices and would follow females into their burrows to mate – where they would often cannibalize the pups that they found. At the end of the 16 months, Calhoun selected four of the healthiest males and females and moved them into new living conditions – free from the disquieting density of the interconnected pens. They were six months old, in the prime of their rat lives – but he found that they did not recover normal function. The females gave birth to fewer litters than was expected – and none of the young that were born survived to maturity. In all, Calhoun repeated the experiment three times and observed similar results with each repetition. In a second round of experiments, he made some modifications to the food hoppers that produced the behavioral sink and found slightly different outcomes. When provided with powdered food rather than the pellets hidden behind a metal mesh, much of the aggregation behaviors around the food disappeared.

The second round of experiments, without the markings of a behavioral sink. The distribution of males and females is much more distinct in this population – with a greater number of females overall, and a greater disparity visible between sex parity in the different pens. Low numbers of males represents a “territory,” controlled by a single dominant male that drives the other males into neighboring pens. In this second round, it was water that was difficult to get – not food. But for whatever reason – perhaps the lack of dopaminergic effects of drinking water there was less conditioned clustering. The lack of behavioral sinks in the second round of experiments resulted in a much less marked distribution of males and females across the different pens of the experiment – but the behavioral oddities caused by high density remained.”

Abbie Lathrop, Mouse Woman of Granby: Rodent Fancier, Accidental Genetics Pioneer
by Robert A. Kyle, MD, Marc A. Shampo, PhD/ 2010 Nov

Abbie E. C. Lathrop was born in Illinois in 1868, the only child of schoolteachers who were originally from Granby, MA. Few details about her childhood are known. Lathrop was homeschooled for the first 16 years of her life, after which she attended an unidentified academy for approximately 2 years, which allowed her to obtain an Illinois teaching certificate. She taught elementary school for several years but was not successful, apparently because of chronic ill health. Lathrop eventually quit teaching and moved to a farm in Granby in 1900. She initially attempted to start a poultry business, which failed. Her focus then shifted to breeding “fancy” mice and rats, which she marketed to rodent hobbyists and keepers of exotic pets, and later began selling in large numbers to scientific researchers.

“remaining buildings of Granby Mouse Farm of Miss Abbie Lathrop”

She also raised guinea pigs, rabbits, and ferrets. Some of her guinea pigs were purchased by the US government and used to detect toxic gases in the trenches of World War I battlefields. Two of Lathrop’s close friends, Ada Gray and Edith Chapin, assisted in her animal business, and the women also employed many neighborhood children to clean cages and feed oats and crackers to the animals. Lathrop kept careful breeding records, which proved helpful for researchers. At one point, her farm housed more than 11,000 mice. Several years after Lathrop developed her mouse colonies, she noticed that some of the animals were developing unusual skin lesions. She sent samples to several prominent scientists asking for help. Renowned experimental pathologist Leo Loeb (1869-1959), then at the University of Pennsylvania, became interested in the problem and diagnosed the lesions as malignant. His correspondence with Lathrop developed into an ongoing research collaboration that continued until her death. Loeb suggested several experiments related to cancer that Lathrop then carefully performed at her farm.

“Pages from Lathrop’s scientific notebooks are held at the Jackson Laboratory”

Their mutual work resulted in 10 coauthored articles in prominent journals, such as the Journal of Experimental Medicine and the Journal of Cancer Research. Among other important observations, Lathrop and Loeb established that susceptibility to mammary tumors varied between different strains of mice and that ovariectomy reduced the incidence of mammary tumors. William Ernest Castle (1867-1962), a pioneer in mammalian genetics who was among the first to realize the potential power of mouse models for human disease, bought some of Lathrop’s mice for his laboratory in 1902, a fertile time for genetic research immediately after the rediscovery of the now-famous pea experiments of the Moravian monk Gregor Mendel. Castle directed the Bussey Institute for Biological Research at Harvard University for more than 30 years, and he trained most of the leaders in the early mammalian genetics field, including Nobel Laureate George D. Snell (1903-1996) and Clarence Cook (“C.C.”) Little (1888-1971). Little, in turn, founded a facility in Bar Harbor, ME, now known as the Jackson Laboratory, which remains one of the world’s most important sources of inbred strains of laboratory mice. The most frequently used laboratory mouse strain for the past 80 years, C57BL/6J (“Black 6”), is derived from one of Lathrop’s animals—mouse number 57—bred by Little. The complete genomic sequence of the C57BL/6J mouse was reported in 2002.

…Although the cartoon characters Mickey and Minnie Mouse have been honored philatelically hundreds of times by many countries, only a few postage stamps have featured real mice or other rodents, probably because of the poor reputation that rodents have had among humans for thousands of years. Ancient Egyptians, for example, revered cats because cats kept grain stores free of mice and other “vermin.” The US Postal Service included the deer mouse in a 1987 series of 50 stamps featuring North American wildlife (Scott No. 2324). However, the deer mouse (genus Peromyscus) — the primary reservoir species for hantavirus and a vector for transmission of several other infections including Lyme disease, babesiosis, and bubonic plague — is used for laboratory experiments less frequently than strains of the common house mouse (Mus musculus).”

Of mice and men and low unit cost, by James R. Griesemer & Elihu M. Gerson  /  2006
Making mice: Standardizing animals for American biomedical research, 1900–1955. by Karen A. Rader

Making mice is a contribution to scientific biography, to the history of laboratory model organisms, and to the historiography of scientific standardization. The heart of the story is the development of standardized mice (i.e. genetically inbred strains) for use in cancer research, basic mammalian genetics, and other allied lines of work. One theme is the work of learning how to create such strains through careful breeding and husbandry. Another is building the organization which can produce and distribute strains on a fairly substantial scale. This organization was (and is) both a world of volunteers and a formal bureaucracy. A third part of the story is the development of alliances with significant players and social worlds—the medical cancer research world, mouse fanciers, animal rights people, government agencies, private philanthropic foundations and individuals, the press, and consumers of biomedical products and services. Rader’s argument is organized around the story of Clarence Cook Little’s career as a mammalian geneticist at the dawn of American genetics.

She follows Little from his student days inbreeding mice to produce genetic homogeneity, sparring with fly geneticists like Sturtevant and Morgan over the interpretation of data, and becoming interested in the relevance of inbred mice to the study of cancer. Little’s career took him from junior scientist–administrator at Cold Spring Harbor, to president of two universities, and finally to founding director of the Jackson Memorial Laboratory in Bar Harbor, Maine.

A curious coda to Little’s life of science entrepreneurship, upon his retirement in 1956, was his position as science advisor to the Tobacco Industry Research Council. Little’s career is intertwined both with the institutional and organizational biography of the Jackson Lab and with that of Mus musculus, the domestic house mouse, in its own career path from pest and pet to mass produced, standardized, genetically purified, specialized laboratory ‘tool’ or ‘reagent’ for American biomedical science. During Little’s lifetime, ‘the mouse’ became a model organism for the genetics of cancer, tumor transplantation, immunogenetics, and radiation biology.

“C.C. Little in front of burned out buildings after the 1947 Jackson Laboratory fire”

2. C. C. Little and the Jackson laboratory
Clarence Cook Little (1888–1971) was a student at Harvard during the first decade of the twentieth century, just as genetics was becoming a new discipline. His undergraduate interest in dog breeding shifted to mouse genetics under the tutelage of pioneer mammalian geneticist William Castle. Little continued at Harvard as a graduate student with Castle at the Bussey Institute of Applied Biology to become one of the first mouse geneticists, focusing on the development of inbred strains for the Mendelian analysis of coat and eye color mutations. Little brought mice into the laboratory and contributed to their transformation into laboratory materials, as C. W. Woodworth, F. W. Carpenter, and F. J. Moenkhaus (Castle students) and F. E. Lutz (influenced by Castle’s inbreeding studies with fruit flies), were doing for Drosophila (Allen, 1975).

Little’s work began, not with ‘wild’ caught flies on window ledges, but with animals purchased from mouse fanciers, whose interests in exotic coat colors and whose commercial husbandry practices provided a ready source of raw materials. Little’s early interest in standardization of research materials can be traced to his undergraduate project. Johannsen’s theory of pure lines appeared in 1909, implying genotypic limits to the power of natural selection and raising new questions about effects of inbreeding (Johannsen, 1909). Inbreeding was thought to lead to genetic homogeneity and to potentially harmful side effects such as reduced fertility. But homogeneity could also be viewed as genetic purity, sustainable by careful husbandry practices and controlled inbreeding. With the rise of genetics as a new analytic discipline in biology, geneticists argued that genetically pure or homogeneous materials were needed in all kinds of biological research to disentangle genetic from other kinds of effects (e.g. Morgan 1926).

So, if the side effects were tolerable, inbreeding could become a means of genetic purification of research materials and thus the basis for standardizing genetic backgrounds against which to carry out various kinds of scientific work. By the time Little completed his graduate work on mouse coat color genetics (and after failing his exams in 1912), he became established as a mouse geneticist, introducing Mendelian nomenclature for strains derived from the fanciers (p. 41). Little’s interests, however, were already shifting to the use of mice for cancer research. Studies of spontaneous tumors in mice were linked to genetic questions by E. E. Tyzzer, director of the Harvard Cancer Commission of the US Public Health Service. Tyzzer examined susceptibility to tumors as a result of tissue transplanted between mouse strains.

Little attempted to interpret Tyzzer’s results in terms of a Mendelian multifactor explanation of cancer susceptibility and argued that such results would only be interpretable if the strains used were genetically homogeneous (an argument that Thomas Hunt Morgan extended in 1926 to the study of developing embryos generally). This argument for genetic purity of research materials became central to Little’s lifelong scientific and entrepreneurIal agendas. Little went to work for Tyzzer for a short while before serving in the military during World War I and then taking a position in 1919 at Cold Spring Harbor’s Station for Experimental Evolution, which was founded by Charles Davenport, Castle’s mentor (p. 50). At Cold Spring Harbor, Little continued his cancer interests, but also began the organizing activities that eventually transformed his skills as an ‘inbreeder’ into those of a manufacturer of purified mice and purveyor of standards.

He started the Mouse Club of America in 1920 to formalize the exchange of information and material for scientific mouse breeding. In 1922, Little’s career took an administrative turn when he accepted the presidency of the University of Maine and then three years later the presidency of the University of Michigan. Four years after that, Little left academia to found the Jackson Memorial Laboratory in 1929. In all three places, Little attempted to continue his genetics work while complementing his research activities with ‘educational experimentation’. Little’s work as a university president introduced him to the elites of Detroit and Bar Harbor, Maine. His growing contacts with individual and institutional patrons such as the Rockefeller Foundation, but particularly Roscoe B. Jackson (whom Little met at Bar Harbor), help explain Little’s challenges and also his successes as an organizer and institution builder. Jackson was a founder of the Hudson Motor Car Company of Detroit. He was in a financial position to support Little’s summer field course in Bar Harbor (p. 66) and eventually to bankroll the eponymous laboratory.

Little’s struggle to gain institutional backing depended on convincing patrons like Jackson of the general scientific significance and public health value of linking genetics work with the popular public cause of curing cancer. Laboratory systems using mice (and a few other mammals) would link genetics with human biology. An emphasis on rigorous and systematic experimental evidence, which could only be produced from inbreeding practices like his own, would make Little’s inbred mice standards for mammalian laboratory research. To Little, linking basic genetics and public goods such as cancer research (and eugenics) with a plan to deliver standardized inbred mice in quantity to the scientific community was the proper way forward. Such arguments to patrons and scientists alike paved the way for Little’s move to Maine and the founding of the Jackson Laboratory.

Roscoe Jackson helped Little raise funds for his mouse laboratory among wealthy automaker friends, for example Edsel Ford, during their summers in Bar Harbor, Maine. Little was preparing to leave Michigan in frustration over his lack of success in research and faculty opposition to his educational reform proposals. Two events were pivotal in the founding of the lab, both of them financial. First, Roscoe Jackson died of flu in 1929, and although his widow and Detroit friends supported Little’s move to Bar Harbor to construct a small, independent laboratory for mammalian genetics and cancer research, he had lost a key ally and patron. Second, the stock market crash of 1929 occurred on the eve of the lab’s opening (p. 96). The Great Depression severely reduced the private wealth available for scientific philanthropy at the moment that flu carried off Little’s most effective private patron. Little travelled a rocky road to financial stability. Rader’s narrative focuses on a surprising symmetry of the contingencies of Little’s journey: the very same travails of funding explain both his successes and his failures in building and maintaining the laboratory, in cancer research, and in entrenching ‘JAX mice’ as laboratory standards.

By 1932, private funding for the Jackson Laboratory had run out and renewed support was not forthcoming due to the depression. The lab had focused on launching its research programs on the genetics of spontaneous tumors in inbred mice in these early years, but financial distress compelled Little to accept a US Public Health Service contract to provide it with mice in order to keep the laboratory going (p. 100). Economic pressure rather than research productivity drove the redistribution of resources toward scaled-up animal production, Rader argues, in contrast to the Morgan school’s fruit fly program, (see Kohler 1994). Scaling up did not impel Little toward a commercial model of animal production, however. He favored traditional, cooperative exchange of materials as a service to the community of researchers.

Indeed, many mice were shipped free of charge, even as the depression deepened and his funding dried up. Later, when the Lab was sued over its tax exempt status, Little defended its practices on grounds that they certainly could have made money as a commercial operation, but did not. Rader’s argument is that economic necessity was the contingency driving Little toward the notion that producing mice for sale could be more than ‘mere animal caretaking work’ (p. 114). Entering an agreement with Howard Andervont and J. W. Schereschewsky at the US Public Health Service to buy Jackson mice for their cancer research seemed to Little like selling out his scientific ideal of free exchange of research material, not a commercial opportunity as it would have appeared to a businessman of science like Henry Ward of Ward’s Natural Science Establishment (Ward, 1948). At times, Rader’s story reads like a B-movie in which impending disaster seems evident to all but the central protagonist. Little could have turned to mouse production as a commercial venture—that was what his laboratory seemed good at, so what held him back? What made the research ideal sufficiently powerful to steer Little in ways that frustrated his own success time and again?

While Rader’s narrative captures Little’s story, and the story of the Jackson Lab, a full portrait of what made Little tick is not on offer in this book or indeed in this biographical genre of laboratory organisms. Selling the number and quality of mice required by the PHS contract was critical to the transformation of Jackson mice into a standard of purity. Mice were to come from a specified tumor stock and be raised in the same environment as the parental stock (p. 120). The sales contract thus required a level of specificity and quantification in the exchange of material absent from the informal and smaller scale exchanges with individual scientists. Coupled with Little’s argument that only Jackson could implement the controlled husbandry conditions required, the PHS contract entrenched Jackson’s procedures in PHS research protocols and created opportunities and incentives for economies of scale and ‘powerful imperatives for embracing businesslike values of efficiency and organization’ (p. 123). The decision to make mice available to the PHS generated demand that compelled scaling up.

This then changed the focus of production to the development of standards. Notice that these were standards of purity, quality, and continuity, not standardized mice in the conventional sense in the research community that a particular strain was best and most desirable for research. Standardization, in other words, concerns the substitutability of mouse ‘products’ in a research consumer’s usage. That is, standardization is about what happens when one ‘plugs in’ a purified, specialized mouse into a research process (experiment, breeding program). If one such mouse is substitutable for another, then the mouse meets a standard of purity. If husbandry practices and breeding protocols yield mice meeting particular standards of genetic purity, then one might also consider the practices and protocols to be standards as well. The promulgation of such a standard throughout a research community (research market), depends on the substitutability of mice within a given research project.

The capacity to supply such standardized mice reliably on a large scale (i.e. to multiple research programs) requires a kind of industrial organization different from, if complementary to, the production of specialized pure strains for particular research programs. In 1937, a printed listing of mouse stocks included six different popular strains, and also their value for various kinds of scientific work. Articulation of genetic nomenclature for the varied mouse strains Jackson was producing, together with PHS notation for tumor types, served to standardize strain names, even though they arose from a highly contingent (and, Little thought, temporary) funding arrangement (p. 127). Rader quotes Little’s application to the Rockefeller Foundation, emphasizing that ‘material produced under standardized conditions will eliminate variables and make more practicable comparison or repetition of work in or between different laboratories’ (p. 163).

The conditions are standardized and rendered repeatable, while the materials are purified and specialized (by inbreeding) to take on particular value for specified kinds of work such as ‘general laboratory work’, ‘genetic research’, ‘breast and internal tumor incidence’. The Mouse Newsletter, edited by Jackson scientist George Snell, served to standardize experimental nomenclature as it advertised the producers of inbred strains from many sources besides JAX, but also emphasizing that only JAX had them all (p. 170). And in 1941, ‘JAX Mice’ were registered with the US Patent Office.

Thus, JAX mice became a standard in the context of a system of standardized practices and procedures for producing, distributing, and caring for inbred mice. Moreover, the difficulties of maintaining husbandry conditions at the receiving end led Little to regiment mouse food, laboratory protocols (in a manual), and wooden shipping boxes. That is, in order for research consumers to produce stable, reliable, and repeatable results, their husbandry practices had to be standardized as well. Just as VCR or DVD ± RW standards for recording media are worthless if consumers lack equipment that can read them, genetic purity in a specialized JAX mouse is worthless if researchers cannot achieve phenotypic performance of husbanded mice comparable to those advertised by the Jackson Laboratory.

As the depression deepened, Little continued to promote the value of Jackson Laboratory research in the search for a cancer cure. But by 1937, Jackson Lab was providing more mice for other and diverse research needs than it had to the PHS (p. 133). It’s important to note that the mice themselves became standards only with respect to specialized lines of work calling for particular inbred strains. Rader’s conclusion, that ‘The construction of a reliable mechanism through which researchers could obtain and use inbred mice helped transform the inbred mouse into a standard animal, both in terms of it being ‘‘widely available’’ and ‘‘widely used’’ ’ (p. 174), elides the role of particular inbred strains. The mechanism producing ‘the inbred mouse’ resulted first in a standard of purity, while the particular strains are of value because they are specialized for different kinds of study. The mice of each strain are standardized, that is, substitutable for a given project; the different strains are specialized. Mice from one strain are, in general, not substitutable for those from another strain. Specialization and standardization trade off against one another to some extent; a strain tuned precisely to the need of a particular research program will not be suitable for a wide variety of programs even though they are produced by the same industrialized methods of breeding and husbandry.

One of Rader’s more interesting arguments concerns the rationalization of research in the early twentieth century, which broadly reorganized around analytic problems (such as heredity, development, and geographical distribution) rather than taxon characteristics (Gerson, 1998). One became a transmission geneticist rather than a botanist, entomologist, or mammalogist. Rader focuses her attention to rationalization on the changing funding context from individual patrons such as Jackson, to private bureaucracies, such as the Rockefeller foundations.

The concerns of the latter spanned many lines of work and soon came to promote the virtues of coordination and consistency (Kohler, 1991). The shift to public funding that began in the 1930s accelerated this tendency. The law creating the National Cancer Institute in 1937, for example, provided a new constituency and organizational impetus to Little’s pursuit of the inbred mouse as a standard research tool. This was critical to the Jackson Lab financially since Little’s attempts to gain substantial support from the Rockefeller Foundation had mixed success: the RF only seemed interested in supporting ‘retail’ mouse production for small scale mammalian genetics at Jackson, in contrast to the ‘wholesale’ fly program it supported at CalTech (p. 145). Little’s connection of mouse genetics to cancer was opportune but risky, as public demand for a cure rose alongside a movement against animal experimentation.

The balance of interests tipped toward biomedicine and against experimentation in the case of rodents, however. Little’s rhetoric shifted the Laboratory’s focus from research more squarely onto standardization: mice as interchangeable parts, mice as ‘chemically pure animals’, standardized mice serving the democratic ideal of accountability to scientific peers. A key turning point detailed by Rader was the decision by the Surgeon General’s National Advisory Cancer Council to support a National Cancer Institute grant to the Jackson Lab in 1937, through which ‘the organizational suitability of inbred mice for experimental cancer research became official federal policy’ and JAX mice a de facto ‘industry standard’, since the Jackson Lab was the only large scale provider until after World War II (p. 160). One major argument of the book seems best summed up on pages 175–180. There, Rader observes that Little’s dedication to a genetic explanation of cancer prevented him from taking the research steps necessary to explore alternatives, for example, viral or other acquired causes of cancer, in part because he felt discovery of non-genetic explanations might undermine the argument for JAX mice as genetically pure reagents for cancer research.

Differently put, Little’s argument for genetic research into cancer led to taking on the project of purification and standardization, and as the institutional arrangements were put in place to achieve those goals, they supplanted cancer as the primary reason a genetic approach was required. Patrons, however, supported the Jackson Lab’s research primarily as an indirect means of promoting the supply of JAX mice as standard laboratory tools or purified reagents and repeatedly withdrew funding of this precariously justified cancer research. Each time Little had to scramble for renewed financial support, the JAX standards for mouse breeding and husbandry ratcheted up and became more entrenched. Philosophers of science have rightly argued that the pursuit of ‘false models’ can lead to ‘truer theories’ (Wimsatt, 1987). Perhaps Little’s story is one of unintentionally discovering that false models—his genetic model of cancer—can also lead to truer research standards. Each time the financial plug was pulled from Little’s vision of inbred mice as a genetically purified standard for cancer research, he gained knowledge of how to entrench the mouse standard a little deeper, even if it meant a shifting array of audiences, allies, and markets for his mice: geneticists, tumor researchers, chemotherapists, and radiation biologists.

Mouse production increased more than tenfold from the 1930s through World War II. By 1947, Little was again making the case to the Rockefeller Foundation for support, but the argument had fully shifted away from research: Little’s latest request was to fund buildings to house mouse production. Little contrasted the ‘simple and quiet surroundings where resources are concentrated on a single objective and the complex and confused environments of great universities where competitive interests continually arise’ (p. 207). As a locus of material production for research, the Jackson Laboratory made a uniquely valuable contribution. Rockefeller granted the funds. On 23 October 1947, a fire killed fourteen people and tens of thousands of mice, destroyed the original laboratory, and damaged two of the new ‘mouse houses’ (p. 1). Economic contingencies, once again, were pivotal for Little and the Lab. The fire drew national attention to the Lab, giving huge publicity to its mice and their role in biomedical research, and completing the transformation of Jackson Laboratory into a production facility rather than a research organization, the center of a materials network rather than a ‘center of calculation’ (Latour 1987). Mouse stocks were rebuilt after the fire, in part, through gifts of breeding pairs of mice sent back to JAX by individual researchers.

At the same time, the obsolescence of Little’s ‘paternalist’ pre-war managerial style (p. 215) became evident as the rebuilt laboratory became fully the ‘bureau of mouse standards’ the Rockefeller Foundation thought it to be (p. 216). In the 1950s, JAX standards became commercialized when cancer therapeutic drug development came under the coordination of the federal Cancer Chemotherapy National Service Center. The demand for mice to be used in screening led to outsourcing of mouse production to commercial suppliers following JAX inbreeding protocols. A final post-war development described by Rader in Making mice was the advent of radiation biology. The study of induced mutations and radiation risk became big research business and mice became key test organisms for radiation genetics. The ‘mega-mouse project’ of Liane and Willliam Russell (a former JAX researcher and student of Sewall Wright) at Oak Ridge National Laboratories in Tennessee attempted to produce and measure mutation rates due to ionizing radiation. This ‘mission oriented’ biomedical research under the aegis of the Atomic Energy Commission and organized on the model of the Manhattan Project relied on a particular specialized mouse strain, SLT. The scale of the mega-mouse project virtually guaranteed that SLT would become a mouse standard for mutation studies and, in conjunction with the scale up of federal research on radiation, ensure that Jackson Laboratory standards for inbred mice would become deeply entrenched in American biomedical research.

3. Historiography of standardization in science
Although Making mice is not strictly a biography of Little, his organizational drive, entrepreneurial spirit, business acumen, and social network are key to Rader’s description of Little’s surprisingly rapid career trajectory over a decade. Rader identifies a fundamental shift in support for scientific research in America at this time, from small individual grants to ‘programmatic funding for cooperative discipline-building’ (p. 61). She also details Little’s need to scale up his mouse breeding operations during the period of his university presidencies in order to stabilize them from the threat of epidemics or chance losses in transit. The scaling up problem focuses attention on the story of mouse standardization in a different way from other organism biographies. Her project is not so much a shift of attention from scientist to model organism as an entwining of the careers of scientist, laboratory, and mouse. Rader’s narrative offers an historiographic counterpoint to the recent spate of organism biographies of rats (Clause, 1993), corn (Kimmelman, 1992), flies (Kohler, 1994), nematodes (Ankeny, 1997), and viruses (Creager, 2002). In these, Rader argues, scientists appear to quick march under the banner of efficient, productive model organisms and Taylorized laboratory systems straight to the heart of core problems of twentieth-century theoretical and applied biology.

Rader takes these narratives to assume that standardization of organisms in combination with universal scientific norms is prerequisite to the success of rationalized modern science. Instead, she argues that such standards are consequences rather than causes of scientific consensus (p. 15). She notes that in experimental biology, the material and practical aspects of standardization are ‘synchronic’, so a nuanced story of local and highly contingent institutional and organizational arrangements is needed to account for the emergence of standardized organisms. Rader’s project addresses a paradox of Little’s role in the biographies of the mouse and the Jackson Lab ‘mouse house’. Although genetically specialized inbred JAX mice became the ‘gold standard’ of biomedical research by mid-century and the laboratory became the ‘National Bureau of Mouse Standards’, the research projects for which Little promoted the mouse model and with which his laboratory pursued a genetic model of mammalian cancer were not particularly successful, raising questions about the historical alignment of scientific research with discipline and institution building. ‘In other words’, Rader writes, ‘how did the genetically standardized mouse initially succeed as a standard organism when mammalian genetics, the very science for which it was supposedly best designed, initially did not?’ (p. 17).

Rader’s solution begins by noting the connection between medieval and early modern meanings of ‘standard’. The latter and now common meaning of ‘an object or quality that serves as the authorized basis or principle to which others conform or by which they are judged’ (p. 16), must be complemented, she argues, with an older notion of a standard originating in warfare: ‘a conspicuous object, such as a banner, carried at the top of a pole and used to mark a rallying point’ (p. 17). Rallying biomedical science around genetically pure mice in order to pursue problems of cancer biology was Little’s institutional goal. His cartoon representations of the mouse for scientists and the public (illustrated throughout the book) include an effort to initiate a joint 25th anniversary celebration with that other famous rodent, Mickey Mouse. Such efforts testify to Little’s use of the mouse as a rallying standard bearer. However, his success as an entrepreneur and cheerleader, aided by connections with elite patrons developed during his days as a university president, was complemented by failure as a cancer geneticist.

Rader’s achievement is to draw attention to the need to follow both aspects in telling the story of the standardization of the laboratory mouse. Had Little succeeded as a researcher, his mouse standardization enterprise might well have failed. Rader plots contours to make a topographic map of Little’s scientific campaign, putting the analyst of science in a better position to interpret the contingent elevations and local depressions of scientific work in the broadest sense as at once laboratory practice, organization building, and alliance formation. This approach appeals because linear narratives of the march of scientific progress along predefined roads mapped out by universal scientific norms of improved precision, accuracy, objectivity, and truth are clearly not up to the task of analyzing a history of standardization. Traditional biography offers few resources for a contextually aware science studies. In that sense, Rader’s book is a success. In the course of mapping the terrain, however, Rader offers scant comparative interpretation of her data to advance beyond the historiographic traditions she criticizes, despite her ambitious introductory chapter laying out historiographic and analytical goals. The epilogue draws together elements of her chosen landscape into a much needed inventory, but far from an effective analytical model. This lacuna is not unexpected because the value of Rader’s historical data for science studies lies ultimately in a fully comparative social analysis, which would have doubled the book’s size and changed its analytical focus from biography—of a man, an organization, and a model organism—to sociology of science. Thus, we can applaud Rader’s historical data and historiographic turn and at the same time wish for a more developed assessment of their significance.

‘To understand how broader cultural imperatives shaped the practical nature of standardization in research, and vice versa’ (p. 7), the local contingencies and alliances in Little’s scrappy, entrepreneurial struggle to keep the Jackson Lab alive must be evaluated and weighed against other stories only cited or briefly mentioned by Rader, with different circumstances and contexts. Rader explores in detail the ways in which the mass production of specialized mice became a financial imperative for the Jackson Lab and thus the proverbial tail wagging Little’s dogged and marginally successful pursuit of the genetic basis of cancer. The Great Depression, the shifting priorities of the Rockefeller Foundation, relations with medical school researchers, the founding of the National Cancer Institute with its various mandates for biomedical research—all these are critical features in the landscape Rader maps. At the same time, we need to understand in rich detail the laboratory projects and practices of Little and his colleagues and how they were transformed by Little’s use of the mouse as a standard bearer for his genetic model of cancer. We learn from Rader that the mouse became standardized because it was used as a standard bearer, but not exactly what a standard mouse ‘looks’ like, precisely what it is to be standardized (in the sense of substitutable), or what the evidence is that the mouse truly is standardized, rather than merely common across the several disciplinary specialties in which Little and his colleagues worked.

Rader’s evidence shows that JAX mice spread, but without evaluation of other sources and patterns of contemporary mouse production and use, the social place and economic position of JAX mice remains uncertain. By analogy, learning that Apple Computer grew to become a multibillion dollar company over twenty years has one meaning, but learning that its market share declined by an order of magnitude over the same period has a different meaning. For example, in Chapter 5, Rader points out that by 1947, JAX inbred mice were not universally used, ‘but JAX’s distribution network and product recognition had generated a reliable constituency, especially in cancer research’ (p. 181). This shows that JAX mice were specialized and frequently used, but not that they constituted a standard for laboratory mice. Her quantitative data tell the same story: use of inbred mice rose from less than one percent of studies in the journal Cancer Research in 1932 to over thirty percent in 1937 to about seventy percent in 1947 (pp. 181–182). However, the market share of JAX mice is unknown. (Rader notes that Jackson Lab was not unique in its mouse breeding goals, even at the time the lab was set up, p. 99.)

Whether the important story is JAX product placement or rather the spread of inbreeding as a standardized protocol instead of a JAX mouse standardized reagent requires more extensive comparative analysis. If ‘[e]xisting narratives beg larger questions about the underlying values motivating the process of adopting standardized animals and other model systems at the bench-top’ (p. 15), Rader’s narrative leaves unclear how the bench-top protocols and practices Little developed out of classical husbandry practices and classical genetic techniques articulate with projects and problems of standard bearing and concepts of standardization in the various social worlds in which Little and JAX participated. Rader need not be faulted. She has taken great pains to reconstruct JAX’s financial vicissitudes, which is central to the problem of articulating Little’s entrepreneurship with mouse standardization. But at the same time, it is harder to understand from Rader’s account why Little’s program for mammalian cancer research at Jackson Lab failed to sustain that institution than, for example, from Kohler’s account, why Morgan’s fly lab transmission genetics and linkage mapping program became a self-sustaining ‘breeder reactor’ (Kohler, 1994). Or indeed why Little seems to have had such a difficult time accepting or even recognizing that the research line he took was unsuccessful and that his dogged pursuit of a marginal line of work was fundamentally unsustainable in the context of a private, non-profit research institution rather than a university, industrial, or government agency laboratory. Or, perhaps that is the story: maybe only an entrepreneur with a vision powerful enough to mask his scientific inadequacy could keep a marginal institution alive long enough to become entrenched as a standard bearer and standards producer in the face of a failing scientific program and a worse business plan.”

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