Seeing What the Naked Eye Can’t

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These images show living neurons colored green and dead neurons colored yellow. Jeremy Linsley, CC BY-NC-ND

Automated microscopes, for example, have made it possible to take time-lapse images of cells, resulting in massive amounts of data that require manual sifting. Neuroscientist Jeremy Linsley and his team encountered this dilemma in their own work on neurodegenerative disease. They’ve been relying on an army of interns to scour hundreds of thousands of images of neurons and tally each death—a slow and expensive process.

Centuries ago, scientists and artists examined plants, animals, and anatomy through illustration. Sketches of unfamiliar species in their natural environments aided in their classification, and drawings of the human body advanced the study of its structure and function. With the help of the printing press, these artistic renderings—which later included the view under the lenses of early microscopes—popularized scientific knowledge about the natural world.

Researchers have been charting the brain by stitching together multiple snapshots like a photo mosaic. They use different techniques to label a specific cell type and then image the whole brain at high resolution. Layer by layer, each run-through creates an increasingly detailed and more complete model. Neuroscientist Yongsoo Kim likens the process to a satellite image of the brain. Combining millions of these photos allows researchers to zoom into the weeds and zoom out to a bird’s-eye view.

The microscope is an iconic symbol of the life sciences, and for good reason. From the discovery of the existence of cells to the structure of DNA, microscopy has been a quintessential tool of the field, unlocking new dimensions of the living world not only for scientists but also for the general public.

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“That those images and videos are often beautiful is an added benefit,” she writes.

But building a map of a city, however detailed, isn’t the same as understanding its rhythm and atmosphere. Likewise, knowing where every cell is located relative to each other doesn’t necessarily tell researchers how they function or interact. Just as important as charting out the landscape of an organ is coming up with a working theory of how it all fits together and performs as a whole. Right now, Kim notes, analysis lags behind technical advances in data collection.

Cryo-electron tomography shows what molecules look like in high resolution—in this case, the virus that causes Covid-19. Nanographics, CC BY-SA

“By taking out human guesswork, (AI models) increase the reproducibility and speed of research and can help researchers discover new phenomena in images that they would otherwise not have been able to easily recognize,” writes Linsley.

4. Seeing as appreciating

This selection of stories from The Conversation’s archive presents a few ways in which microscopy has contributed to different forms of scientific knowledge, including techniques that take visualization beyond sight altogether.

1. Seeing as identifying

These techniques not only generate images at or near atomic resolution but also preserve the natural shape of difficult-to-capture biomolecules of interest. Researchers were able to use cryo-EM, for instance, to capture the elusive structure of the protein on the surface of the shape-shifting hepatitis C virus, providing key information for a future vaccine.

Further enhancements to science’s visual acuity will reveal more of the fine details of the building blocks of life.

Although hand drawings have since given way to advanced imaging techniques and computer models, the legacy of communicating science through art continues. Scientific publications and BioArt competitions highlight laboratory images and videos to share the awe and wonder of studying the natural world with the general public. Using visualizations in classrooms and art museums can also promote science literacy by giving students a chance to look through the eye of the microscope as a scientist would.

They also opened the black box of the model to figure out how it was finding dead cells, revealing new signals of neuron death previously unknown to researchers because they weren’t obvious to the human eye.

Microscopy images are often framed as snapshots—circumscribed parts of a whole that have been magnified to reveal their hidden features. But nothing in an organism works in isolation. After discerning individual components, scientists are tasked with charting how they interact with each other in the macrosystem of the body. Figuring this out requires not only identifying every component that makes up a particular cell, tissue, and organ but also placing them in relation to each other; in other words, making a map.

The abstract qualities of science can be made tangible in ways that don’t involve sight. Proteins, for instance, can be translated into music by mapping their physical properties into sound: amino acids turn into notes, while structural loops become tempos and motifs. Computational biologists Peng Zhang and Yu Zong Chen enhanced the musicality of these mapping techniques by basing them on different music styles, such as that of Chopin. Consequently, a protein that prevents cancer formation, p53, sounds toccata-like, and the protein that binds to the hormone and neurotransmitter oxytocin flutters with recurring motifs.

Biologist and BioArt Awards judge Chris Curran believes that making visible the processes and concepts of science can grant a greater depth of understanding of the natural world necessary to being an informed citizen.

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