What it feels like to kill 563 mice for science
Breeding, modifying and killing mice has helped scientists make incredible discoveries about human biology. But that doesn't mean sacrificing them is easy.
Editors' note: This story contains graphic descriptions that may be disturbing to some readers.
You might think of scientists as people in a perfectly ironed, pristine white lab coat with a chest pocket full of pens. "Eureka!" they shout, after mulling on an idea for weeks. "That's how we cure cancer!"
It never works like that.
Despite what films like Jurassic Park want you to believe, scientific research is a process without glamour. A slow burn of small discoveries build up, piece by piece, to a revelation. Sometimes that occurs over years, even decades. Sometimes the discoveries build up to disappointment.
OK, often they build up to disappointment.
And when your research involves the routine killing of small animals, science can also feel harsh and even unfair.
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As a Ph.D. student studying pharmaceutical and medical science, I killed 563 mice over four years. Killing mice became part of my life.
Eat, sleep, kill, repeat.
At the University of South Australia, I studied how vitamin D is metabolized by the skeleton to promote growth and strength in adulthood. You can't just sacrifice human beings, remove and study their bones, but -- with ethics approval -- you can do so with mice. So, every few weeks, I'd head to the university's animal housing facility, carrying a bucket of ice and surgical tools.
The first thing you have to do when you prepare to kill a mouse is get dressed.
These were the clothes I wore when killing mice: a sky-blue lab gown around my body, a baker's hair net over my scalp, latex gloves on my hands and protective "booties" over my shoes. These prevented me from transporting harmful organisms from the outside world into the purpose-built, sterile facility.
A much more youthful version of myself contemplating one of the experimental mice.
Once you pass the sterilisation checkpoint you're confronted with a wall of cages, stacked floor to ceiling in climate-controlled racks. The air feels light. The smell of animal urine and musk creeps into your nose. An air-conditioner hums a constant tune.
There's the susurrus of mice padding on shredded paper, the wild thrashing of mice wrestling. In each cage, one to six animals are housed, huddling under cut-up cereal boxes, hiding within the safety of toilet roll tubes.
On the front of each cage, a small card gives each mouse a name:365, 28, 192. There are no "Laurens" or "Henrys" here. Just numbers. Numbers that tell you when the mouse was born. And when it's destined to die.
In the last six months, the mice in this room have had their homes cleaned for them, had 24/7 access to water and been fed a specially formulated diet of mouse chow fortified with essential vitamins and minerals. Every day, a technician has monitored their condition, scoring them on a scale that describes how healthy (or unhealthy) they may be.
Today, seven of those mice will be sacrificed for science.
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Killing a mouse efficiently takes practice.
You pull a cage from the wall, cart it down a silent hallway to a room that looks and smells sterile. The sharp scent of isoflurane, the anaesthetic of choice, is so biting you can almost taste it. The mice flee under cardboard as you lift the roof off their home. You locate the mouse scheduled to die, grab it by the tail and move it into a clear, plastic chamber. A tangle of tubes sprawl across the benchtop and connect to valves in the wall.
Opening the valves slowly fills the box with the transparent anaesthetic.
Watching, you can see the mouse's chest pump like a piston as its breathing hastens, fighting for oxygen, before it gradually slows down again.
Asleep.
The anaesthetic gas has two purposes. First, it numbs the mouse to pain without killing it. It also, in this case, allows us to extract blood from the heart while the mouse is still alive, giving us a more accurate picture of the concentration of minerals present in its blood at time of death.
Biologically, mice are quite similar to humans.
It's around this point that you forget about your own breathing. Subconsciously, it's happening. Your lungs filling, emptying, filling, emptying. But you just stop noticing.
You lay the mouse on its back, spread out its limbs and tape them to the work bench. With a pair of surgical scissors you make a small cut just under the rib cage, opening up its chest cavity. Still beating, a heart pulses in front of you, no bigger than the fingernail on your pinky. Upon seeing it for the first time, all the air in your lungs rushes out of your mouth.
Seeing it for the 400th time the edge is dulled, slightly, but you never get comfortable. Your hands don't shake anymore, but your chest still tightens.
A syringe tip plunges in to draw blood. In most cases, 250 microlitres is extracted. Once the bleed is complete, the mouse is killed via cervical dislocation, a technique that severs the connection between the spinal cord and the brain. The accepted way of performing this technique is to place a ballpoint pen or other stick-like object across the back of the mouse's neck, pushing forward and down while simultaneously pulling backward on the creature's tail. To ensure the animal has been euthanized, you must take your forefinger and thumb to feel for empty space between the vertebra and the skull, confirming separation.
It's a final blow designed to provide the animal with a rapid, painless death.
Then the relevant organs are harvested -- that means removing the liver, the kidneys, a section of the small intestine, both femurs, both tibia, the skull and the spine -- and placing them in a tiny plastic canopic jar, ready to freeze. The hollowed-out corpse is dumped into a plastic zip-lock bag, the kind you might keep your lunch in, and thrown in the bin.
Then the procedure begins again, with another mouse.
Maybe once. Maybe twice. Maybe three more times. Every 15 minutes, another carcass, another zip-lock bag, another bin. On this day, seven times. On another day, maybe ten or twelve.
It's always an unpleasant process. A cold, efficient, joyless procedure.
As the final mouse is anaesthetized, it became routine for our laboratory to play Jeff Buckley's song Hallelujah. By the time Buckley croons of the secret chord that David played, our surgical tools are pinching and pulling organs from the last rodent's body and placing them on ice.
For the first time in hours, you remember to breathe.
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Over the last 100 years, mice have become crucial models for medical research.
They're cheap. They're biologically very similar to humans, sharing an extremely similar set of genes. And we understand how they're different, too. They breed quickly and have large litters of offspring. They're small, and thus economical. Compared with us, their lifecycle is condensed into the space of a few years. They're low maintenance, especially when we compare them with other animals used for research, such as rabbits and dogs.
You can easily manipulate their genes to switch molecular pathways and proteins on or off. You can interbreed mice to achieve genetically identical strains.
They're indispensable and yet, disposable. We need them to understand how drugs work in the milieu of chemicals, molecules and proteins that make up a body. Mice teach us how different systems respond to threats or treatments -- something cells in a petri dish simply cannot do.
We've already learned a lot from them. Genetically modified mouse models have shown us how tumours progress and metastasize, highlighted more effective ways to treat autoimmune disease and, in my own research, elucidated how vitamin D interacts with specific bone cells to modulate bone turnover.
Mice are low maintenance, especially when compared with other animals used for research, such as rabbits and dogs.
There exists bountiful evidence that mice are great analogues for human disease, but that doesn't make killing them any easier.
Every kill day was exhausting.
It's hard not to sympathise with an animal that has spent its entire life in a shoebox-sized cage.
I can understand why there's fervent opposition to animal research from organisations like PETA. Its figures suggest over 100 million animals are used and killed for science each year in the US alone. PETA takes exception to the fact that mice are excluded from provisions in the Animal Welfare act designed to protect other species.
While the mice themselves had it much worse than me, a heavy gloom hung over every single kill day. An overbearing weight. It sapped my energy. In the evening, I'd scrub my skin hard enough to leave red flushes, just trying to get the smell of anaesthetic off me.
"This is the only way."
"They don't suffer."
"How else will we know?"
Researchers don't experience some perverse joy from taking an animal's life. In fact, one technician who often assisted me with kills told me that they were only helping because they couldn't bear the thought that someone else might do it -- and do it poorly. All of us -- researchers, students, technicians, supervisors, ethics committees -- are forced to reconcile the idea that killing animals is OK because it makes human beings better off as a species.
Then we sleep and get ready to do it all again.
Just 300 to go.
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Five hundred and sixty-three mice died to bring you this story.
Their existence is only a footnote, recorded in an Excel spreadsheet on a dusty hard drive somewhere at the bottom of a filing cabinet. Yet, every one of them contributed, in some way, to increasing our knowledge of human physiology.
It was Isaac Newton who said, "If I have seen further, it is by standing on the shoulders of giants." Yet it is the mouse that allows us a glimpse into the future of medicine, giving us the opportunity to uncover the molecular mechanisms of human disease and unravel the mysteries of our own biology.
Because of mice, we have seen -- and will continue to see -- further.
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Correction, 5:41 p.m.: Amount of blood drawn via cardiac bleed changed from 25 millilitres to 250 microlitres.