DARPA made it a condition of funding to pair research teams in biotech with independent verifiers, and learned a ton. They talk about bringing more engineering to biosciences. Very encouraging, I hope this catches on.
2023-04-04: The number of problems reproducing mouse studies is daunting. Perhaps more organelles can be part of the solution.

• The Bible of mouse caretaking is called the Guide for Care and Use of Laboratory Animals. It did not change at all between 1972 and 2019, despite everything I’m about to tell you.
• Mice raised at 5 different animal facilities in Europe, under otherwise identical conditions, have “persistent differences in body weight” and behavior. There are even differences in how their genomic DNA is packaged inside of neurons. Nobody really knows why.
• If 2 different scientists at the same university carry out the same experiment on mice, their results will be more replicable than the same experiment, carried out by the same person, at separate universities.
• Mice that give birth in cages with little toys or knick-knacks produce more pups. Those pups are larger after 21 days.
• Smaller cages cause *some* strains of male mice to fight more often. (There’s an entire meta-analysis on this topic alone, which I’m sure you’d find riveting.)
• “Mice housed on deep bedding had smaller adrenal, kidney, liver and heart weights as well as larger body and tail lengths compared with groups kept on shallow bedding” after just 12 weeks.
• Mice handled by male scientists feel less pain. The finding holds true when a female scientist does the experiment but holds a t-shirt, previously worn by a man, near the mouse. The effect fades away after 30 minutes.
• Mice spend less time licking an irritated part of their body when a human is nearby, “even if that ‘person’ is a cardboard cutout of Paris Hilton.”
• Animals stored on higher shelves are more stressed and have impaired immune systems, probably because these areas are closer to lights and vibrate more.
  • Mice on the top shelf of a rack receive 20-80x more light than mice housed at the bottom.
• Mice exposed to even dim light during the night (e.g. an LED on a computer monitor) “had a body mass gain…50% more than other mice that lived in a standard light-dark cycle.”
• After just 4 weeks, mice exposed to a dim light during the night ate more than those in complete darkness. (Mice, like humans, raid the proverbial refrigerator when they can’t sleep.) Many genes linked to inflammation were also activated.
• Mice kept in cages with wood chip bedding eat 1.5 grams of their mattress every day. This changes the bacteria in their microbiomes.
• Historically, male mice were used in research 6x more often than females because they don’t have an estrous cycle, and their metabolisms were therefore thought to be more predictable. About 80% of drugs are tested only on male mice. Some drugs, notably Ambien, are more potent in females and cause more side effects.
• Female mice are less erratic than males while exploring an open space. The estrous cycle of female mice shows only “a very weak effect on their behavior.” Other scientists have said much the same thing since at least 2018.
• The body temperature and activity patterns of male mice vary more in “a day than females do across an entire estrous cycle.”
• 6% of all mouse genes are regulated in sex-specific ways. The expression level of 1k genes varies between males and females, and the level of another 600 genes wobble, up and down, during a female’s estrous cycle.
  • The genes turned on in a specific type of immune cell, called a neutrophil, also differ between males and females.
• The genes associated with longer lifespans in mice differ between males and females, based on data from “3k genetically diverse animals raised in tightly-controlled, homogenous conditions.”

• Grain-based food usually contains unknown amounts of phytoestrogens, which change the onset of an animal’s puberty.
• The standard diet for mice, called AIN-93, hasn’t changed in 30 years. But manufacturing of that food does: Even if you use “the same grain-based diet used in the past by others, its composition will likely differ.”
• The sexes of a mouse’s siblings can skew an animal’s behavior. “Female-skewed litters demonstrated more social play, while the male-skewed litters demonstrated more solitary play.”
• Rooms with a higher humidity are associated with lower pain thresholds for mice scorched with hot water. Nobody really knows why.
• Most animal facilities change the bedding for mice every week, which causes “heart rate, blood pressure, and locomotion in both male and female mice” to spike for between 75 – 105 minutes. This effect persists even after mice have been moved many times.
• Mice exposed to a regular, 37 Hertz magnetic field spend less time exploring open spaces, and more time sleeping.
• Mice are kept in rooms between 21 and 26 degrees Celsius. “But the natural comfortable temperature for mice is warmer — between 30 and 32 degrees Celsius.” Colder mice experience more stress, their tumors grow faster than mice kept in warm rooms, and “mice genetically modified to develop obesity only gained a lot of weight at warmer temperatures but not at colder temperatures.”
• Keeping mice at higher temperatures also blunts their muscle gain after exercise.
• 2 mice of the same strain are often genetically distinct, even if they’re labeled as isogenic. DNA differences accumulate over generations of breeding.
• Sometimes, scientists use the entirely wrong mice, or swap 2 mouse strains accidentally, and have to retract their papers afterward.
• The microbiome of an animal can influence the effects of a drug. In 1 instance, a lab at Michigan State University was “testing how a certain drug affects bone density, and they found that treated lab mice lost bone compared with controls.” When they repeated the experiment on identical mice, of the same strain and from the same vendor, those mice gained bone density. A 3rd experiment found no effect. Each animal had a different microbiome.

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