Best laid plans / Of mice and their whiskers
The bleak white tiles that cover everything but the ceiling, made further painful by the immaculate neon lighting, demand to be covered in some way, even if only to signal the non-threatening nature of the facility. It is after all where the university’s evolutionary biology department is housed, nothing to be scared of. But as you venture further inside, the scene becomes more animated, with proud displays of scientific research, flyers for lectures, photos from conferences. In the northern wing of the fourth floor, there is an office where posters and notes have spilled over their intended pinboards. In between geeky comic strips about pipetting, there’s black stickers of mouse outlines. I somehow remember the quote: “the best laid plans of mice and men often go awry.” Close by, a photo of a mouse printed so large, that what is naturally a three and a half inch rodent is now my size. The entire display is endearing. Perhaps reminiscent of an adolatory, teenager-obsessed-with-boy-band behavior, but endearing. And as my imagination runs wild with visions of The Beatles eating yellow slices of cheddar, an interruption: “You’re looking for Jake?”
I first met Jake Gable in late 2016, when he was part of the teaching staff of a course titled “Understanding Darwinism”, and I was a wide-eyed freshman. I remember his introduction: he’s from Washington, he likes peanut butter and he studies the whiskers of mice. About three and a half years later, it’s easy to recognize each other, even if I now bear the dark half-moons of sleepless college nights under my eyes and he is sporting a moustache, some faux-whiskers of his own. This morning, he is at his desk, looking at blue and black figures on his computer; my guess is they’re microscope images.
Unlike the choice of styling one’s facial hair, most of our traits have developed over time, carrying an evolutionary reasoning and lineage. From our thumbs to our toes, we owe our features to their hereditary character and the wonders of our adaptive nature. Scientists operate under the assumption that every hair on an animal’s body has a purpose.
“I like learning about all these different animals and all these different forms that they have evolved into, hence the question, why do we have all of this diversity?”
If you stop to think about it, a lot of known things we take for granted are actually “these crazy adaptations” that Jake likes to talk about. Sweat for example. Humans do it as evaporative cooling, a trick we only share with horses. And while other mammals stop and pant to exhaust heat, we can breathe through our mouths and keep exercising. It’s fascinating to see what extra-oddities we’ve developed, but there are some trait clubs we have been excluded from.
“Humans are the only mammals that do not have whiskers.” Well, that can’t possibly be true! By now, I have followed Jake into another room, where he works when he wants to be alone. He grabs a marker and heads to the whiteboard, drawing phylogenetic trees, diagrams of organisms' evolutionary relations to one another. Some other drawings are still up, he says he’d been figuring out research details. “Let me correct myself: mammals at some point split into two, eutherian mammals that give live placental births and monotremes that don’t. Like the platypus or the echidna. Humans are the only eutherian mammals that don’t have whiskers. Even mammals that don’t have them as adults, like the dolphins, have whisker follicles early in life. A vestigial trait from their ancestors who had and used whiskers.” Vestigial traits, from the word vestige, are obsolete remnants found in a species’ present form. We humans have a coccyx, wisdom teeth, the goosebumps reflex, to name a few.
With so many species under the Mammalia class, Jake headed to the museum in the first weeks of his PhD and looked at hundreds of specimens from different sorts of populations. He chose peromyscus maniculatus, the deer mouse. “They’re thought to be the most common and widespread small mammal in North America. I can watch them in the wild and have them in the lab, I can also track them through multiple generations.” A practical choice!
“There is another important detail... the background, I guess: mice will actively sweep their whiskers around.” He extends his long fingers into jazz hands to mimic movement. I’m puzzled. “Most mammals have static whiskers, something has to move or brush against them. Mice and other rodents have musculature in their snout so they can whisk while standing.” I giggle. I would have imagined that act as being, if anything, whiskering. Jake does not seem as amused, whisking is serious business. And rightfully so. Teams of engineers are trying to replicate whisking for robots, to map textures, surfaces and to stealthily navigate in the dark.
He’s been studying the whiskers of deer mice for 6 years now, has been part of multiple projects and has done enough research and experiments to write a series of books - a young expert in the field. But his biggest focus has been their length. Deer mice are split into forest mice and prairie mice, and with virtually no other differences, the forest mice have longer whiskers. What determined such a discrepancy in the whisker length of these populations? And which gene is responsible for it? A month before he becomes Dr. Gable, Jake is finishing a close analysis of the whisker follicle structure of both forest and prairie mice. I’ve seen him work before, but I’m most excited about today’s agenda. “To the lab!”
The Biology Laboratories on Harvard’s campus are something of a maze. More than once have I felt utterly lost in the halls, but also outside, in between the buildings and those courtyards with tricky dead-ends. I can’t say for sure, but there might have been someone with a pair of binoculars on one of the higher floors, observing and mockingly taking notes on my behavior. Jake laughs, says he doubts it. His experiments with mice have been quite different from the cinematographic depictions of labyrinths and cheese.
During the first three years, one of his studies involved mice making their way over a ledge. “Would length have some significance to the mice in navigating their environments?” There were ramps, ledges, an infrared camera, a room in pitch-black darkness, the mice and our scientist. It was called the gap crossing test, and the subject would climb up, sense the gap, extend its small snout out until the whiskers touched the next ledge, before reaching out with its front legs. There were 38 of the little performers, half prairie, half forest, and Jake would get to know each one over the first several weeks, while he varied the gap distance and watched them learn. He became sure the length was crucial. “So I trimmed their whiskers.”
In all of this, I continue to wonder at the amount of meticulous labor. How do you measure, trim, follow differences in something so small? Buckets of patience and a unique set of skills, turns out. “I had to quickly learn how to hold the mouse with one hand, pinch the back of their neck, hold their tail between my pinky and ring finger, belly out. It’s a very niche skill, but I can easily identify individual whisker positions and measure them with digital calipers.” There’s incredible gentleness in how he’s holding the invisible mouse. “When I track whisker growth, I paint each whisker with UV-fluorescent dye.” It takes a while. Once at a conference, another researcher was not convinced that Jake was measuring the same whiskers every time. The photos of differently dyed ones shut him up.
The lab is big, and at noon, light is flooding in. I follow him towards one end and enter an annex with 10 freezers. He opens the middle one and, as I’m gawking at the large drawers, pulls out a small ball of aluminum foil. We walk to the other side of the lab and sit down in front of a microtome. The machine is basically an enormous deli slicer. Jake carefully unwraps the ball and inside I see a bit of iced medium and a dark brown speck. “I extracted this whisker follicle a while back, but I don’t like some of the images I took of it, so I have to redo it today.” He places the medium with the speck inside the machine in a sort of sealed chamber. The indicator above it shows -20 degrees Celsius. I can’t keep track of all the levers and wheels he touches to set everything in place, until he pauses. “This gives me a 16 microns thick vertical slice,” and he rotates a small wheel to the side. An imperceptible movement of a blade to the follicle. Jake takes a glass rectangle and lightly touches the slice. Before staining, it has to go back in the freezer for a couple of hours.
YouTube provides a plethora of videos of wild deer mice, hopping around fallen leaves. Some clips are time lapses of rescued litters. A pink manicured lady is holding a mouse pup between her fingers. It can’t be bigger than an olive in the first shots, one day after its birth. There’s a full collection of whiskers already adorning the tiniest snout.
I ask if he sees the mice colonies these days. “Sometimes, but I mostly have a lab technician watching them now.” Do they bite? “Yeah, they do. We start the colonies from these wild populations. Working with domesticated mice is much chiller than these guys. These guys will try to bite you or cause chaos. It’s funny, what you learn is that you think you’ll have designed your behavioral arena to account for any possible situation, try to contain the mouse to make sure it’s doing what you want it to do. But deer mice will always find some flaw in your system, to escape and screw it up. I haven't been bitten in a while. I learned.” There’s an unmistakable tone of admiration when he talks about them, a well mixed potion of fascination, excitement and care. When we discuss the coming end of the project, it sprinkles in some exhaustion and nostalgia.
The slide is frozen, and I watch Jake slouch over it at a workbench. He carefully applies a series of weird liquids and explains it’s to fix the tissue so it won’t degrade. Next up, something to make the tissue permeable. And finally, fluorescent reactive dye that “attaches to certain things, you’ll see.” He moves really quickly, washes the slide and sets it to dry. I know some people say that pet owners take after their pets, and I’m thinking of this theory as I watch Jake move restlessly through the lab. Maybe it extends to what one studies too. We’re ready to look at the section now, and I follow him into a smaller room. He turns off the lights and the monitor screen and microscope glow in the dark. “I’ve spent a lot of days here, my eyes adjust quickly.” As an astronomer, I keep up well.
If the forest mouse whiskers are longer, there are only so many possibilities: the prairie and forest could grow at different rates, whiskers could start growing sooner, stop later, and so on. Jake measured his 40 rodents every day for 60 days. Newborn mice had whiskers, but were too small to be accurately measured. He had to follow the growth another way and the answer starts at the follicle, seen through slides like the one he is now placing under the microscope. It’s bright blue against a black background on the screen.
“Whiskers are, after all, specialized hairs, keratinized cells with a hair follicle. And at the base of the follicle there is something called a dermal papillae, the structure that controls the growth. See this mass of blue dots? It marks dividing cells, so we can see it happening. Similarities with regular hair stop here, because these parts,..” he switches lights on the microscope and now new areas on the image are highlighted in red “..are part of larger structures called blood sinuses. They’re like capsules and they make the whisker follicle and base more rigid, and therefore more sensitive to disturbances. They’re highly innervated too.” We switch more lights and go in depth about the morphology and numerous components of the follicle. An un-updated LinkedIn photo taught me Jake once sported light blue hair, while a Facebook one taught me he plays guitar and has a bandcamp. But as we’re leaning over zoomed in photos of a single brown speck, he whispers explanations about every structural detail. The system is way more complex than I could have imagined. “I think it’s better looking through the microscope directly,” he advises and I squint into the viewer.
When we emerge out of the microscope’s room, daylight has been switched to fluorescent. We walk back to his office to see the images on the computer, and it becomes clear that we might have outlasted other scientists. At his desk, there are too many papers around and too many open tabs on the screen. I think about everything I’ve learned today, in the past weeks, and Jake’s work seems never ending.
“I’m looking for gene expression patterns, I want to narrow it down to one responsible gene governing this trait. Mice have about 24,000 genes, and around 16,000 of those will be expressed in the whisker follicle. My shortlist is at about 14 now; aiming to go through it in the next year, I’m staying after my thesis defence to finish some other projects.” I think he senses my amazement tarnished by fatigue. “I know it’s hard, really hard. Folks in the future will come up with very clever ways to go through this process, but with our technology and whatnot, it’s a long, arduous road to get from trait to gene.”
I’m coming to see Jake again next week. We’ll be looking at data related to that list of 14, as he continues the ascent up the mountain of research he has risen on the tip of a whisker.
