tag:theconversation.com,2011:/us/topics/microscope-50112/articlesMicroscope – The Conversation2023-08-22T12:25:22Ztag:theconversation.com,2011:article/2116662023-08-22T12:25:22Z2023-08-22T12:25:22ZSeeing what the naked eye can’t − 4 essential reads on how scientists bring the microscopic world into plain sight<figure><img src="https://images.theconversation.com/files/543356/original/file-20230817-17-593vu4.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2048%2C1839&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">This microscopy image shows the retina of a mouse, laid flat and made fluorescent.</span> <span class="attribution"><a class="source" href="https://flic.kr/p/Mr9Ybe">Kenyoung Kim, Wonkyu Ju and Mark Ellisman/National Center for Microscopy and Imaging Research, University of California, San Diego via Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p>The microscope is an iconic symbol of the life sciences – and for good reason. From the discovery of the <a href="https://theconversation.com/robert-hooke-the-english-leonardo-who-was-a-17th-century-scientific-superstar-119497">existence of cells</a> to the <a href="https://theconversation.com/sexism-pushed-rosalind-franklin-toward-the-scientific-sidelines-during-her-short-life-but-her-work-still-shines-on-her-100th-birthday-139249">structure of DNA</a>, 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.</p>
<p>For the life sciences, where understanding the function of a living thing often requires interpreting its form, imaging is vital to confirming theories and revealing what is yet unknown.</p>
<p>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.</p>
<h2>1. Seeing as identifying</h2>
<p>Over the past few centuries, the microscope has undergone a gradual but significant evolution. Each advance has allowed researchers to see increasingly smaller and more fragile structures and biomolecules at increasingly higher resolution – from cells, to the structures within cells, to the structures within the structures within cells, down to atoms.</p>
<p>But there is still a resolution gap between the smallest and largest structures of the cell. Biophysicist <a href="https://scholar.google.com/citations?user=MZ6qrPUAAAAJ&hl=en">Jeremy Berg</a> drew an analogy to Google Maps: Though scientists could see the city as a whole and individual houses, they couldn’t make out the neighborhoods. </p>
<p>“Seeing these neighborhood-level details is essential to being able to understand how individual components work together in the environment of a cell,” he writes.</p>
<p>Scientists are working to bridge that resolution gap. Improvements to the 2014 Nobel Prize-winning <a href="https://theconversation.com/zooming-across-time-and-space-simultaneously-with-superresolution-to-understand-how-cells-divide-203324">superresolution microscopy</a>, for example, have enhanced the study of lengthy processes like cell division by capturing images across a range of size and time scales simultaneously, bringing clarity to details traditional microscopes tend to blur.</p>
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<a href="https://images.theconversation.com/files/543350/original/file-20230817-29-4xyjde.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Cryo-ET image of SARS-CoV-2" src="https://images.theconversation.com/files/543350/original/file-20230817-29-4xyjde.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/543350/original/file-20230817-29-4xyjde.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=508&fit=crop&dpr=1 600w, https://images.theconversation.com/files/543350/original/file-20230817-29-4xyjde.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=508&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/543350/original/file-20230817-29-4xyjde.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=508&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/543350/original/file-20230817-29-4xyjde.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=639&fit=crop&dpr=1 754w, https://images.theconversation.com/files/543350/original/file-20230817-29-4xyjde.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=639&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/543350/original/file-20230817-29-4xyjde.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=639&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Cryo-electron tomography shows what molecules look like in high resolution – in this case, the virus that causes COVID-19.</span>
<span class="attribution"><a class="source" href="https://nanographics.at/projects/coronavirus-3d/">Nanographics</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<p>Another technique, <a href="https://theconversation.com/visualizing-the-inside-of-cells-at-previously-impossible-resolutions-provides-vivid-insights-into-how-they-work-195873">cryo-electron microscopy, or cryo-EM</a>, won a Nobel Prize in 2017 for bringing even more complex, dynamic molecules into view by flash-freezing them. This creates a protective glasslike shell around samples as they’re bombarded by a beam of electrons to create their photo op. Cryo-ET, a specialized type of cryo-EM, can construct 3D images of molecular structures within their natural environments. </p>
<p>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 <a href="https://theconversation.com/scientists-uncovered-the-structure-of-the-key-protein-for-a-future-hepatitis-c-vaccine-heres-how-they-did-it-193705">shape-shifting hepatitis C virus</a>, providing key information for a future vaccine.</p>
<p>Further enhancements to science’s visual acuity will reveal more of the fine details of the building blocks of life. </p>
<p>“I anticipate seeing new theories on how we understand cells, moving from disorganized bags of molecules to intricately organized and dynamic systems,” writes Berg.</p>
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Read more:
<a href="https://theconversation.com/visualizing-the-inside-of-cells-at-previously-impossible-resolutions-provides-vivid-insights-into-how-they-work-195873">Visualizing the inside of cells at previously impossible resolutions provides vivid insights into how they work</a>
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<h2>2. Seeing as scoping</h2>
<p>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.</p>
<p>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 <a href="https://scholar.google.com/citations?user=WOQx1ksAAAAJ&hl=en">Yongsoo Kim</a> likens the process to a <a href="https://theconversation.com/mapping-how-the-100-billion-cells-in-the-brain-all-fit-together-is-the-brave-new-world-of-neuroscience-170182">satellite image of the brain</a>. Combining millions of these photos allows researchers to zoom into the weeds and zoom out to a bird’s-eye view.</p>
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<a href="https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Stiched high-resolution microscopy image of mouse brain." src="https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Zooming in on this image of a mouse brain reveals rectangular lines where images were stitched together, with each colored dot representing a specific brain cell type.</span>
<span class="attribution"><a class="source" href="http://kimlab.io">Yongsoo Kim</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
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<p>But building a map of a city, however detailed, is not 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.</p>
<p>“Incredibly rich, high-resolution brain mapping presents a great opportunity for neuroscientists to deeply ponder what this new data says about how the brain works,” Kim writes. “Though there are still many unknowns about the brain, these new tools and techniques could help bring them to light.”</p>
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Read more:
<a href="https://theconversation.com/mapping-how-the-100-billion-cells-in-the-brain-all-fit-together-is-the-brave-new-world-of-neuroscience-170182">Mapping how the 100 billion cells in the brain all fit together is the brave new world of neuroscience</a>
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<h2>3. Seeing as recognizing</h2>
<p>Every improvement in technology brings a parallel improvement in the data it collects, both in quality and in quantity. But that data is only useful insofar as researchers are able to analyze it – high granularity isn’t helpful if those details aren’t appreciable, and high output isn’t beneficial if it’s too overwhelming to organize.</p>
<p>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 <a href="https://scholar.google.com/citations?hl=en&user=cQdBoWUAAAAJ&view_op=list_works&alert_preview_top_rm=2&sortby=pubdate">Jeremy Linsley</a> 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.</p>
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<a href="https://images.theconversation.com/files/443244/original/file-20220128-14047-1wva32o.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscopy images showing rat neurons before and after treatment with glutamate; the neurons are colored green when alive and yellow when dead" src="https://images.theconversation.com/files/443244/original/file-20220128-14047-1wva32o.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/443244/original/file-20220128-14047-1wva32o.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=354&fit=crop&dpr=1 600w, https://images.theconversation.com/files/443244/original/file-20220128-14047-1wva32o.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=354&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/443244/original/file-20220128-14047-1wva32o.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=354&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/443244/original/file-20220128-14047-1wva32o.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=445&fit=crop&dpr=1 754w, https://images.theconversation.com/files/443244/original/file-20220128-14047-1wva32o.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=445&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/443244/original/file-20220128-14047-1wva32o.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=445&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">These images show living neurons colored green and dead neurons colored yellow.</span>
<span class="attribution"><a class="source" href="https://doi.org/10.1126/sciadv.abf8142">Jeremy Linsley</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
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<p>So they turned to artificial intelligence. Researchers can train an AI model to recognize specific patterns by feeding it many sample images, pointing out structures of interest and extrapolating the algorithm to new contexts. Linsley and his team developed a model to <a href="https://theconversation.com/new-ai-technique-identifies-dead-cells-under-the-microscope-100-times-faster-than-people-can-potentially-accelerating-research-on-neurodegenerative-diseases-like-alzheimers-174154">distinguish between living and dead neurons</a> with greater speed and accuracy than people trained to do the same task. </p>
<p>They also opened the <a href="https://theconversation.com/what-is-a-black-box-a-computer-scientist-explains-what-it-means-when-the-inner-workings-of-ais-are-hidden-203888">black box</a> of the model to figure out how it was finding dead cells, revealing new signals of neuron death that researchers previously weren’t aware of because they weren’t obvious to the human eye.</p>
<p>“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.</p>
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Read more:
<a href="https://theconversation.com/new-ai-technique-identifies-dead-cells-under-the-microscope-100-times-faster-than-people-can-potentially-accelerating-research-on-neurodegenerative-diseases-like-alzheimers-174154">New AI technique identifies dead cells under the microscope 100 times faster than people can – potentially accelerating research on neurodegenerative diseases like Alzheimer's</a>
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<h2>4. Seeing as appreciating</h2>
<p>Even before they had the instruments to zoom in on samples, researchers had a tool in their arsenal to study the living world that they still use today: art.</p>
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<a href="https://images.theconversation.com/files/543351/original/file-20230817-7317-pfm7di.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Illustration of cells in a cork from Robert Hooke's Micrographia" src="https://images.theconversation.com/files/543351/original/file-20230817-7317-pfm7di.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/543351/original/file-20230817-7317-pfm7di.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=875&fit=crop&dpr=1 600w, https://images.theconversation.com/files/543351/original/file-20230817-7317-pfm7di.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=875&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/543351/original/file-20230817-7317-pfm7di.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=875&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/543351/original/file-20230817-7317-pfm7di.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1100&fit=crop&dpr=1 754w, https://images.theconversation.com/files/543351/original/file-20230817-7317-pfm7di.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1100&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/543351/original/file-20230817-7317-pfm7di.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1100&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">This illustration from Robert Hooke’s ‘Micrographia’ shows the structure of cells in a cork.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Micrographia_Schem_11.jpg">Robert Hooke/National Library of Wales via Wikimedia Commons</a></span>
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<p>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 study of its structure and function. With the help of the printing press, these artistic renderings – which later included the <a href="https://www.gutenberg.org/ebooks/15491">view under the lenses</a> of early microscopes – popularized scientific knowledge about the natural world.</p>
<p>Though hand drawings have since given way to advanced imaging techniques and computer models, the legacy of communicating science through art continues. Scientific publications and <a href="https://theconversation.com/art-illuminates-the-beauty-of-science-and-could-inspire-the-next-generation-of-scientists-young-and-old-168925">BioArt competitions</a> 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.</p>
<p>Biologist and BioArt Awards judge <a href="https://www.researchgate.net/profile/Christine-Curran">Chris Curran</a> 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. </p>
<p>“That those images and videos are often beautiful is an added benefit,” she writes.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/ajuxeOly2UE?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">This video of cells migrating in a zebra fish embryo won first place in the 2022 Nikon Small World in Motion Competition.</span></figcaption>
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<p>And the abstract qualities of science can be made tangible in ways that don’t involve sight. Proteins, for instance, can be <a href="https://theconversation.com/the-music-of-proteins-is-made-audible-through-a-computer-program-that-learns-from-chopin-168718">translated into music</a> by mapping their physical properties into sound: amino acids turn into notes, while structural loops become tempos and motifs. Computational biologists <a href="https://scholar.google.com.sg/citations?user=Ic2nqDsAAAAJ&hl=en">Peng Zhang</a> and <a href="https://scholar.google.com/citations?user=784B-f0AAAAJ&hl=en">Yuzong Chen</a> 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.</p>
<p>Framing scientific images as art often requires no more than a change in perspective. And uncovering the poetry of science, many researchers would agree, can help reveal the artistry of life.</p>
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Read more:
<a href="https://theconversation.com/art-illuminates-the-beauty-of-science-and-could-inspire-the-next-generation-of-scientists-young-and-old-168925">Art illuminates the beauty of science – and could inspire the next generation of scientists young and old</a>
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Visualization is an essential part of the scientific process. Advances in imaging have enabled eye-opening discoveries, not only for scientists and researchers but also for the general public.Vivian Lam, Associate Health and Biomedicine EditorLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2033242023-07-20T12:30:22Z2023-07-20T12:30:22ZZooming across time and space simultaneously with superresolution to understand how cells divide<figure><img src="https://images.theconversation.com/files/531154/original/file-20230609-17-rkdph4.png?ixlib=rb-1.1.0&rect=8%2C0%2C1355%2C1245&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">This image of actin filaments in a cell was taken using a type of superresolution microscopy.</span> <span class="attribution"><a class="source" href="https://flic.kr/p/SNa523">Xiaowei Zhuang, HHMI, Harvard University, and Nature Publishing Group/NIH via Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span></figcaption></figure><p><a href="https://www.britannica.com/science/cell-biology/Cell-division-and-growth">Cell division</a>, or the process of how daughter cells emerge from a mother cell, is fundamental to biology. Every cell inherits the same protein and DNA building blocks that make up the cell it originally came from. Yet exactly how these molecular building blocks arrange themselves into new cells has remained a mystery. </p>
<p>Studying cell division requires simultaneously viewing nanometer-scale macromolecules like proteins and DNA all the way up to millimeter-scale populations of cells, and over a time frame that ranges from seconds to weeks. <a href="https://doi.org/10.1002%2F0471142301.ns0201s50">Previous microscopes</a> have been able to capture tiny objects only in short time frames, typically just tens of seconds. There hasn’t been a method that can examine a wide range of size and time scales all at once.</p>
<p>My team <a href="https://scholar.google.com/citations?user=kpr2nocAAAAJ&hl=en">and I</a> at the University of Michigan’s <a href="https://bioplasmonics.org/home.html">Bioplasmonics Group</a> developed a <a href="https://doi.org/10.1038/s41467-023-39624-w">new kind of superresolution imaging</a> that reveals previously unknown features of how cells divide.</p>
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<a href="https://images.theconversation.com/files/523124/original/file-20230427-24-3i5rey.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Illustration depiecting superresolution over time as an hourglass, where the bottom shows a protein and the top a dividing cell going from unresolved to resolved" src="https://images.theconversation.com/files/523124/original/file-20230427-24-3i5rey.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/523124/original/file-20230427-24-3i5rey.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/523124/original/file-20230427-24-3i5rey.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/523124/original/file-20230427-24-3i5rey.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/523124/original/file-20230427-24-3i5rey.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/523124/original/file-20230427-24-3i5rey.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/523124/original/file-20230427-24-3i5rey.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This hourglass depicts the process of superresolution over time, where the bottom shows a protein and the top a dividing cell going from unresolved, at left, to resolved, at right.</span>
<span class="attribution"><span class="source">Somin Lee</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>Advancing superresolution imaging</h2>
<p>It wasn’t possible to view cells at the molecular level until recently with the <a href="https://www.nobelprize.org/prizes/chemistry/2014/press-release/">2014 Nobel Prize-winning</a> development of superresolution. </p>
<p>Traditional light microscopes <a href="https://courses.lumenlearning.com/suny-physics/chapter/27-6-limits-of-resolution-the-rayleigh-criterion/">blur very small objects</a> that are close together in a sample, because light spreads out as it moves through space. With superresolution, fluorescent probes attached to the sample could be switched on and off like twinkling stars on a clear night. By collecting and combining many images of these probes, a superresolution image can bring very small objects into view. Superresolution opened a whole new world in biology, revealing structures as small as 10 nanometers, which is about the size of a protein molecule. </p>
<p>However, the fluorescent probes that this technique relies on can quickly wear out. This limits its use in studying processes that take place over extended periods, such as cell division. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/537565/original/file-20230714-16543-rjw3zm.gif?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Two blue blobs, one at the bottom left and one at the top right, are separated by pink and blue specks on a black background." src="https://images.theconversation.com/files/537565/original/file-20230714-16543-rjw3zm.gif?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/537565/original/file-20230714-16543-rjw3zm.gif?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=276&fit=crop&dpr=1 600w, https://images.theconversation.com/files/537565/original/file-20230714-16543-rjw3zm.gif?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=276&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/537565/original/file-20230714-16543-rjw3zm.gif?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=276&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/537565/original/file-20230714-16543-rjw3zm.gif?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=347&fit=crop&dpr=1 754w, https://images.theconversation.com/files/537565/original/file-20230714-16543-rjw3zm.gif?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=347&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/537565/original/file-20230714-16543-rjw3zm.gif?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=347&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This PINE microscopy image shows cells dividing, their nuclei stained blue.</span>
<span class="attribution"><a class="source" href="https://doi.org/10.1038/s41467-023-39624-w">Somin Lee/Nature Communications</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>My research team and I have a developed a solution we call <a href="https://doi.org/10.1038/s41467-023-39624-w">PINE nanoscopy</a>. Instead of absorbing light as traditional fluorescent probes do, the probes we use scatter the light so they do not break down with repeated light exposure.</p>
<p>To resolve very small objects that are close together, we built filters made of thin layers of polymers and liquid crystals that allow for detection of scattered light, which triggers the probes to switch on and off. This allowed us to see nanometer-scale details of cells that would otherwise be blurred by traditional microscopes.</p>
<p>Remarkably, we found that these nanometer-scale details could be viewed for very long periods – over 250 hours. These details would typically be lost over time with traditional superresolution methods.</p>
<h2>Shedding new light on cell division</h2>
<p>We then applied our method to study how molecular building blocks organize in cell division. </p>
<p>We focused on a <a href="https://www.britannica.com/science/actin">protein called actin</a> that helps maintain cell structure, among many other functions. Actin is shaped like branching filaments, each about 7 nanometers (millionths of a millimeter) in diameter, that link together to span thousands of nanometers. Using PINE nanoscopy, we attached scattering probes to actin to visually follow human cells as they divided.</p>
<p>We made three observations on how actin building blocks organize during cell division. First, these molecular building blocks expand to increase their connections to their neighbors. Second, they also draw closer to their neighbors to increase their points of contact. And third, the resulting networks tend to contract when the actin molecules are more connected to one another and expand when they are less connected to one another.</p>
<p>Based on these findings, we were able to <a href="https://doi.org/10.1038/s41467-023-39624-w">discover new information</a> about the process of cell division. We found that interactions between actin building blocks sync up with the contraction and expansion of the whole cell during division. In other words, the behavior of the actin molecules is connected to the behavior of the cell: The cell contracts when the actin expands, and it expands when the actin contracts.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/J2_wdNT4KyM?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Superresolution microscopy won the 2014 Nobel Prize in chemistry.</span></figcaption>
</figure>
<h2>Uncovering disease with superresolution</h2>
<p>We plan to use our method to study how other molecular building blocks organize into tissues and organs. Like cells, tissues and organs are <a href="https://courses.lumenlearning.com/wm-biology2/chapter/levels-of-organization-of-living-things/">organized in a hierarchy</a> that can be examined from a scale of small to large. Examining the dynamic and complex process of how protein building blocks interact with one another to form larger structures could advance the future creation of new replacement tissues and organs, such as skin grafts. </p>
<p>We also plan to use our imaging technique to study how protein building blocks become disorganized in disease. Proteins organize into cells, cells organize into tissues and tissues organize into organs. A very small change in building blocks can <a href="https://www.ncbi.nlm.nih.gov/books/NBK9963/">disturb this organization</a>, with effects that can lead to diseases like cancer. Our technique could potentially help researchers visualize and, in turn, better understand how molecular defects in tissues and organs may develop into disease.</p><img src="https://counter.theconversation.com/content/203324/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Somin Lee receives funding from the Air Force of Scientific Research (AFOSR) and National Science Foundation (NSF). </span></em></p>Superresolution microscopy allowed researchers to view cells at the molecular level. Improvements on the technique can help study the building blocks of complex cell processes over time.Somin Lee, Assistant Professor of Electrical & Computer Engineering, Biomedical Engineering, University of MichiganLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1958732023-01-06T13:30:53Z2023-01-06T13:30:53ZVisualizing the inside of cells at previously impossible resolutions provides vivid insights into how they work<figure><img src="https://images.theconversation.com/files/501408/original/file-20221215-16-mtk39u.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1078%2C913&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Cryo-electron tomography shows what molecules look like in high-resolution – in this case, the virus that causes COVID-19.</span> <span class="attribution"><a class="source" href="https://nanographics.at/projects/coronavirus-3d/">Nanographics</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>All life is <a href="https://www.khanacademy.org/science/biology/intro-to-biology/what-is-biology/a/what-is-life">made up of cells</a> several magnitudes <a href="https://learn.genetics.utah.edu/content/cells/scale/">smaller than a grain of salt</a>. Their seemingly simple-looking structures mask the intricate and complex molecular activity that enables them to carry out the functions that sustain life. Researchers are beginning to be able to visualize this activity to a level of detail they haven’t been able to before.</p>
<p>Biological structures can be visualized by either starting at the level of the whole organism and working down, or starting at the level of single atoms and working up. However, there has been a resolution gap between a cell’s smallest structures, such as the cytoskeleton that supports the cell’s shape, and its largest structures, such as the ribosomes that make proteins in cells.</p>
<p>By analogy of Google Maps, while scientists have been able to see entire cities and individual houses, they did not have the tools to see how the houses came together to make up neighborhoods. Seeing these neighborhood-level details is essential to being able to understand how individual components work together in the environment of a cell.</p>
<p>New tools are steadily bridging this gap. And ongoing development of one particular technique, <a href="https://doi.org/10.1002/1873-3468.13948">cryo-electron tomography, or cryo-ET</a>, has the potential to deepen how researchers study and understand how cells function in health and disease. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/026rzTXb1zw?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Cryo-EM won the 2017 Nobel Prize in chemistry.</span></figcaption>
</figure>
<p>As the former <a href="https://www.science.org/content/article/jeremy-berg-named-science-editor-chief">editor-in-chief of Science magazine</a> and as a <a href="https://scholar.google.com/citations?user=MZ6qrPUAAAAJ&hl=en">researcher</a> who has studied hard-to-visualize large protein structures for decades, I have witnessed astounding progress in the development of tools that can determine biological structures in detail. Just as it becomes easier to understand how complicated systems work when you know what they look like, understanding how biological structures fit together in a cell is key to understanding how organisms function.</p>
<h2>A brief history of microscopy</h2>
<p>In the 17th century, <a href="https://doi.org/10.1098/rsob.150019">light microscopy</a> first revealed the existence of cells. In the 20th century, electron microscopy offered even greater detail, revealing the <a href="https://www.nobelprize.org/prizes/medicine/1974/summary/">elaborate structures within cells</a>, including organelles like the endoplasmic reticulum, a complex network of membranes that play key roles in protein synthesis and transport.</p>
<p>From the 1940s to 1960s, biochemists worked to separate cells into their molecular components and learn how to determine the 3D structures of proteins and other macromolecules at or near atomic resolution. This was first done using X-ray crystallography to visualize the structure of <a href="https://www.historyofinformation.com/detail.php?entryid=3015">myoglobin</a>, a protein that supplies oxygen to muscles. </p>
<p>Over the past decade, techniques based on <a href="https://www.nobelprize.org/prizes/chemistry/2002/press-release/">nuclear magnetic resonance</a>, which produces images based on how atoms interact in a magnetic field, and <a href="https://doi.org/10.1016/j.molcel.2015.02.019">cryo-electron microscopy</a> have rapidly increased the number and complexity of the structures scientists can visualize.</p>
<h2>What is cryo-EM and cryo-ET?</h2>
<p><a href="https://theconversation.com/scientists-uncovered-the-structure-of-the-key-protein-for-a-future-hepatitis-c-vaccine-heres-how-they-did-it-193705">Cryo-electron microscopy, or cryo-EM</a>, uses a camera to detect how a beam of electrons is deflected as the electrons pass through a sample to visualize structures at the molecular level. Samples are rapidly frozen to protect them from radiation damage. Detailed models of the structure of interest are made by taking multiple images of individual molecules and averaging them into a 3D structure.</p>
<p><a href="https://doi.org/10.1038/nmeth.4115">Cryo-ET</a> shares similar components with cryo-EM but uses different methods. Because most cells are too thick to be imaged clearly, a region of interest in a cell is first thinned by using an ion beam. The sample is then tilted to take multiple pictures of it at different angles, analogous to a CT scan of a body part – although in this case the imaging system itself is tilted, rather than the patient. These images are then combined by a computer to produce a 3D image of a portion of the cell. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/501410/original/file-20221215-27-mqhygu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Cryo-ET image of algal chloroplast" src="https://images.theconversation.com/files/501410/original/file-20221215-27-mqhygu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/501410/original/file-20221215-27-mqhygu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=932&fit=crop&dpr=1 600w, https://images.theconversation.com/files/501410/original/file-20221215-27-mqhygu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=932&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/501410/original/file-20221215-27-mqhygu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=932&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/501410/original/file-20221215-27-mqhygu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1172&fit=crop&dpr=1 754w, https://images.theconversation.com/files/501410/original/file-20221215-27-mqhygu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1172&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/501410/original/file-20221215-27-mqhygu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1172&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This is a cryo-ET image of the chloroplast of an algal cell.</span>
<span class="attribution"><a class="source" href="https://dx.doi.org/10.7554/eLife.04889">Engel et al. (2015)</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>The resolution of this image is high enough that researchers – or computer programs – can identify the individual components of different structures in a cell. Researchers have used this approach, for example, to show how proteins move and are degraded inside an <a href="https://doi.org/10.1073/pnas.1905641117">algal cell</a>.</p>
<p>Many of the steps researchers once had to do manually to determine the structures of cells are becoming automated, allowing scientists to identify new structures at vastly higher speeds. For example, combining cryo-EM with artificial intelligence programs like <a href="https://doi.org/10.1038/s41586-021-03819-2">AlphaFold</a> can facilitate image interpretation by predicting protein structures that have not yet been characterized. </p>
<h2>Understanding cell structure and function</h2>
<p>As imaging methods and workflows improve, researchers will be able to tackle some key questions in cell biology with different strategies.</p>
<p>The first step is to decide what cells and which regions within those cells to study. Another visualization technique called <a href="https://doi.org/10.1002/1873-3468.14421">correlated light and electron microscopy, or CLEM</a>, uses fluorescent tags to help locate regions where interesting processes are taking place in living cells.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/501414/original/file-20221215-13-dadsmp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Cryo-EM image of human T-cell leukemia virus type-1 (HTLV-1)" src="https://images.theconversation.com/files/501414/original/file-20221215-13-dadsmp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/501414/original/file-20221215-13-dadsmp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=406&fit=crop&dpr=1 600w, https://images.theconversation.com/files/501414/original/file-20221215-13-dadsmp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=406&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/501414/original/file-20221215-13-dadsmp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=406&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/501414/original/file-20221215-13-dadsmp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=510&fit=crop&dpr=1 754w, https://images.theconversation.com/files/501414/original/file-20221215-13-dadsmp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=510&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/501414/original/file-20221215-13-dadsmp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=510&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This is a cryo-EM image of a human T-cell leukemia virus type-1 (HTLV-1).</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/cryo-em-structure-of-human-t-cell-leukemia-virus-royalty-free-image/1300707029">vdvornyk/iStock via Getty Images Plus</a></span>
</figcaption>
</figure>
<p>Comparing the <a href="https://doi.org/10.1016/j.isci.2018.07.014">genetic difference between cells</a> can provide additional insight. Scientists can look at cells that are unable to carry out particular functions and see how this is reflected in their structure. This approach can also help researchers study how cells interact with each other.</p>
<p>Cryo-ET is likely to remain a specialized tool for some time. But further technological developments and increasing accessibility will allow the scientific community to examine the link between cellular structure and function at previously inaccessible levels of detail. I anticipate seeing new theories on how we understand cells, moving from disorganized bags of molecules to intricately organized and dynamic systems.</p><img src="https://counter.theconversation.com/content/195873/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jeremy Berg does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Many microscopy techniques have won Nobel Prizes over the years. Advancements like cryo-ET that allow scientists to see the individual atoms of cells can reveal their biological functions.Jeremy Berg, Professor of Computational and Systems Biology, Associate Senior Vice Chancellor for Science Strategy and Planning, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1937052022-11-22T13:25:50Z2022-11-22T13:25:50ZScientists uncovered the structure of the key protein for a future hepatitis C vaccine – here’s how they did it<figure><img src="https://images.theconversation.com/files/496217/original/file-20221118-14-r6a8me.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1999%2C1499&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Imaging the proteins on the surface of HCV has been challenging because of the virus's shape-shifting nature.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/hepatitis-c-virus-particles-illustration-royalty-free-illustration/1042127452">Juan Gaertner/Science Photo Library via Getty Images</a></span></figcaption></figure><p>The <a href="https://www.cdc.gov/hepatitis/hcv/index.htm">hepatitis C virus, or HCV</a>, causes a chronic liver infection that can lead to permanent liver scarring and, in dire cases, cancer. It affects around <a href="https://doi.org/10.1007/s42399-020-00588-3">71 million people worldwide</a> and causes approximately 400,000 deaths each year. While <a href="https://www.uptodate.com/contents/direct-acting-antivirals-for-the-treatment-of-hepatitis-c-virus-infection">treatments are available</a> for HCV-related infections, they are expensive, hard to access and do not protect against reinfection. A vaccine that can help prevent HCV infection is a major unmet medical and public health need. </p>
<p>One major reason there hasn’t been an HCV vaccine yet is that scientists have yet to identify the proper antigen, or the part of the virus would trigger a protective immune response in the body.</p>
<p>Decades of research have pinpointed <a href="https://doi.org/10.1038/nrmicro3098">HCV E1E2</a>, the only protein on the surface of the virus, as the most promising vaccine candidate. However, developing an HCV vaccine based on that protein is limited by uncertainty around what it looks like. Knowing the structure of the protein is necessary to figure out how the immune system responds to the virus.</p>
<p>So how do researchers capture the structure of single protein on a shape-shifting virus? </p>
<p>We are researchers who specialize in <a href="https://scholar.google.com/citations?user=Xejfx54AAAAJ&hl=en">microscopy</a> and <a href="https://scholar.google.com/citations?user=iQj9rSwAAAAJ&hl=en">vaccine design</a>. With new technology, we were able to <a href="https://doi.org/10.1126/science.abn9884">visualize the molecular details</a> of this elusive protein, unlocking key insights into how this virus works and offering a potential blueprint for a future vaccine.</p>
<p>This is how we did it.</p>
<h2>Challenges of capturing a shape-shifting virus</h2>
<p>One reason it has been so difficult to capture the structure of the HCV E1E2 protein is that it is both <a href="https://doi.org/10.1016/j.celrep.2022.110859">flexible and fragile</a>. It changes its shape so often and is so easily broken that it’s challenging to purify. </p>
<p>As an analogy, imagine a bowl of spaghetti drenched in tomato sauce. Now imagine trying to take a picture of each individual piece of spaghetti in the same position over time while the bowl is shaking. Hard to do, right? That’s what it was like to image the full E1E2 protein.</p>
<p>There were also <a href="https://doi.org/10.1126/science.1251652">technological barriers</a>. Until recently, available imaging techniques were limited in their ability to view microscopic proteins. <a href="https://chem.libretexts.org/Bookshelves/Analytical_Chemistry/Supplemental_Modules_(Analytical_Chemistry)/Instrumentation_and_Analysis/Diffraction_Scattering_Techniques/X-ray_Crystallography">X-ray crystallography</a>, for instance, is unable to capture molecules that frequently change and shape-shift, like HCV. Moreover, other options, such as <a href="https://chem.libretexts.org/Bookshelves/Analytical_Chemistry/Physical_Methods_in_Chemistry_and_Nano_Science_(Barron)/04%3A_Chemical_Speciation/4.07%3A_NMR_Spectroscopy">nuclear magnetic resonance spectroscopy</a>, required cutting large parts of the protein or chemically manipulating it in a way that would transform its physiological state and potentially alter its function.</p>
<p>So to examine the structure of E1E2, we needed a way to extract and purify, stabilize and trap the entire shape-shifting protein into one configuration.</p>
<h2>How to take a picture of protein</h2>
<p><a href="https://doi.org/10.1038/d41586-020-01658-1">Cryo-EM, or cryo-electron microscopy</a>, is a type of imaging technique that views specimens at cryogenic temperatures, in this case the boiling point of nitrogen: minus 320.8 degrees Fahrenheit (minus 196 Celsius). With temperatures that cold, ice freezes so quickly that it doesn’t have time to crystallize. That creates a beautiful glasslike frame around the protein of interest, allowing an unhindered view of every structural detail. Cryo-EM also requires very little protein to work, reducing the amount of material we would need to purify. </p>
<p>Winner of the <a href="https://www.nobelprize.org/prizes/chemistry/2017/press-release/">2017 Nobel Prize in chemistry</a> and <a href="https://doi.org/10.1038/nmeth.3730">Nature magazine’s 2015 “Method of the Year</a>” award, cryo-EM is superb for imaging biological macromolecules in their native, or natural, state in the aqueous environment of human blood. Cryo-EM was also pivotal for characterizing the <a href="https://doi.org/10.1038/nature17200">structure of the COVID-19 virus</a> and its variants.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/Qq8DO-4BnIY?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Cryo-EM has allowed researchers to see complex proteins they weren’t able to before.</span></figcaption>
</figure>
<p>So how do you take a picture of a protein? </p>
<p>First, we embedded the genetic code to make E1E2 in human cells in a petri dish so we would have sufficient amounts of protein to study. After purifying the protein, we <a href="https://caic.bio.cam.ac.uk/electron-microscopy/SpecimenPrep/PlungeFreezing">plunged it into liquid ethane</a> followed by liquid nitrogen. Liquid ethane is used to freeze the protein because it has a higher boiling point than liquid nitrogen. This means it is able to capture more heat before turning to a gas, allowing the protein to freeze much more quickly than it would in liquid nitrogen and avoid structural damage. </p>
<p>Once the protein was vitrified, or in a glasslike ice state, we were able not just to see its overall structure, but also to capture multiple individual configurations of the protein that it takes when it shape-shifts, including its less stable forms.</p>
<p>At this point, our protein was ready for its close-up. We employed a microscope that <a href="https://www.ccber.ucsb.edu/ucsb-natural-history-collections-botanical-plant-anatomy/transmission-electron-microscope">uses a beam of focused, high energy electrons</a> and a very fancy camera that detects how the elections bounce off the protein’s surface. This created a 2D image that we then mathematically transformed into a 3D model. And that was how we got the coveted “close-up” of HCV’s surface protein. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/jgEQ6A2-liU?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">This video shows the newly identified 3D structure of the E1E2 protein on the surface of the hepatitis C virus. The two main subunits of the protein are colored in pink and blue. Sugar molecules are colored in green.</span></figcaption>
</figure>
<p>Our next step was then to assess the location of each amino acid, or building block of the protein, in 3D space. Because every amino acid has a unique shape, we used a computer program that could identify each one in our 3D map. This allowed us to manually reconstruct a high-resolution model of the protein, one building block at a time.</p>
<h2>A new tool to design an HCV vaccine</h2>
<p>Our 3D map and model of the HCV E1E2 protein supports previous research describing its structure while providing new insights into features that will help pave the way for a long-sought vaccine design against this virus. </p>
<p>For example, our structure reveals that the interface between the two main parts of the protein is stabilized by sugars and hydrophobic patches, or areas that push out water molecules. This creates sticky binding hubs along the protein and keeps it from falling apart – a potential site for protective antibodies and new drugs to target. </p>
<p>Researchers now have the tools to design antiviral drugs and vaccines against HCV infection.</p><img src="https://counter.theconversation.com/content/193705/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Lisa Eshun-Wilson receives funding from the National Science Foundation. </span></em></p><p class="fine-print"><em><span>Alba Torrents de la Peña receives funding from Netherlands Organization for Scientific Research (NWO) Rubicon Grant 45219118. </span></em></p>Using a Nobel Prize-winning technique called cryo-EM, researchers were able to identify potential areas on the hepatitis C virus that a vaccine could target.Lisa Eshun-Wilson, Postdoctoral Scholar in Molecular and Cell Biology, The Scripps Research InstituteAlba Torrents de la Peña, Postdoctoral Fellow in Integrative Structural and Computational Biology, The Scripps Research InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1611822021-06-09T20:00:35Z2021-06-09T20:00:35ZA quantum hack for microscopes can reveal the undiscovered details of life<figure><img src="https://images.theconversation.com/files/405227/original/file-20210608-15-euosju.jpg?ixlib=rb-1.1.0&rect=2%2C17%2C1994%2C1874&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Warwick Bowen</span>, <span class="license">Author provided</span></span></figcaption></figure><p>You’ve probably seen images of scientists peering down a microscope, looking at objects invisible to the naked eye. Indeed, microscopes are indispensable to our understanding of life. </p>
<p>They are just as indispensable to biotechnology and medicine, for instance in our response to diseases such as <a href="https://micro.org.au/news/microscopy-helps-the-covid-19-response/">COVID-19</a>. However, the best light microscopes have hit a fundamental barrier – the bright laser light used to illuminate tiny objects can also destroy them.</p>
<p>In research <a href="https://www.nature.com/articles/s41586-021-03528-w">published in Nature today</a>, our team of Australian and German researchers has shown that quantum technologies offer a solution. We built a quantum microscope that can more gently probe biological samples, which allowed us to observe biological structures that would otherwise be impossible to see.</p>
<p>Creating a damage-evading microscope like ours is a long-awaited milestone on <a href="https://uknqt.ukri.org/resources/publications/">international quantum technology roadmaps</a>. It represents a first step into an exciting new era for microscopy, and for sensing technologies more broadly.</p>
<h2>The problem with laser microscopes</h2>
<p>Microscopes have a long history. They are thought to have been first invented by the Dutch lens-maker <a href="https://en.wikipedia.org/wiki/Zacharias_Janssen">Zacharias Janssen</a> around the turn of the seventeenth century. He may have used them to counterfeit coins. This chequered beginning led to the discovery of bacteria, cells and basically all microbiology as we now understand it.</p>
<p>The more recent invention of lasers provided an intense new kind of light. This made a whole new approach to microscopy possible. Laser microscopes allow us to see biology with truly exquisite detail, 10,000 times smaller than the thickness of a human hair. They were awarded the <a href="https://www.nobelprize.org/prizes/chemistry/2014/summary/">2014 Nobel Prize in Chemistry</a>, and have transformed our understanding of cells and of molecules like DNA within them.</p>
<p>However, laser microscopes face a major problem. The very quality that makes them successful – their intensity – is also their Achilles’ heel. The best laser microscopes use light billions of times brighter than sunlight on Earth. As you might imagine, this could cause serious sunburn!</p>
<p>In a laser microscope, biological samples can become sick or perish in seconds. You can see this happening in real time in the movie of a fibroblast cell below, taken by our team member Michael Taylor.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/oUaKG2m3LNc?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">A cell getting uncomfortable and then dying under a laser microscope.</span></figcaption>
</figure>
<h2>Spooky action at a distance provide the solution</h2>
<p>Our microscope evades this problem. It uses a property called quantum entanglement, which Albert Einstein described as “spooky action at a distance”. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/403506/original/file-20210531-17-1ugf5rz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/403506/original/file-20210531-17-1ugf5rz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=768&fit=crop&dpr=1 600w, https://images.theconversation.com/files/403506/original/file-20210531-17-1ugf5rz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=768&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/403506/original/file-20210531-17-1ugf5rz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=768&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/403506/original/file-20210531-17-1ugf5rz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=965&fit=crop&dpr=1 754w, https://images.theconversation.com/files/403506/original/file-20210531-17-1ugf5rz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=965&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/403506/original/file-20210531-17-1ugf5rz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=965&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Our microscope uses pairs of ‘quantum correlated’ photons to achieve clarity that would be impossible with regular light sources.</span>
<span class="attribution"><span class="source">Aleksandr Kakinen</span></span>
</figcaption>
</figure>
<p>Entanglement is an unusual sort of correlation between particles, in our case between the photons that make up a laser beam. We use it to train the photons that leave the microscope to behave themselves, arriving at a detector in a very orderly fashion. This reduces noise.</p>
<p>Other microscopes need to increase the laser intensity to improve the clarity of images. By reducing noise, ours is able to improve the clarity without doing this. Alternatively, we can use a less intense laser to produce the same microscope performance.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/experiment-shows-einsteins-quantum-spooky-action-approaches-the-human-scale-95372">Experiment shows Einstein's quantum 'spooky action' approaches the human scale</a>
</strong>
</em>
</p>
<hr>
<p>A key challenge was to produce quantum entanglement that was bright enough for a laser microscope. We did this by concentrating the photons into laser pulses that were only a few billionths of a second long. This produced entanglement that was 1,000 billion times brighter than has previously been used in imaging.</p>
<p>When used in a microscope, our entangled laser light provided 35% better image clarity than was otherwise possible without destroying the sample. We used the microscope to image the vibrations of molecules within a living cell. This allowed us to see detailed structure that would have been invisible using traditional approaches.</p>
<p>The improvement can be seen in the images below. These images, taken with our microscope, show molecular vibrations within a portion of a yeast cell. The left image uses quantum entanglement, while the right image uses conventional laser light. As I hope you agree, the quantum image is clearer, with regions where fats are stored within the cell (the dark blobs) and the cell wall (the semi-circular structure) both more visible.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/404726/original/file-20210607-28232-1msffx8.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/404726/original/file-20210607-28232-1msffx8.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=161&fit=crop&dpr=1 600w, https://images.theconversation.com/files/404726/original/file-20210607-28232-1msffx8.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=161&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/404726/original/file-20210607-28232-1msffx8.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=161&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/404726/original/file-20210607-28232-1msffx8.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=202&fit=crop&dpr=1 754w, https://images.theconversation.com/files/404726/original/file-20210607-28232-1msffx8.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=202&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/404726/original/file-20210607-28232-1msffx8.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=202&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Example of quantum enhancement possible with our microscope.</span>
<span class="attribution"><span class="source">Warwick Bowen</span></span>
</figcaption>
</figure>
<h2>Towards applications of quantum sensing technologies</h2>
<p>Quantum technologies are expected to have revolutionary applications in computing, communications and sensing. Australia’s Commonwealth Scientific and Industrial Research Organisation (CSIRO) <a href="https://www.csiro.au/en/work-with-us/services/consultancy-strategic-advice-services/csiro-futures/futures-reports/quantum">estimates</a> they will create an A$86 billion dollar global industry by 2040.</p>
<p>Quantum entanglement underpins many of these applications. A key challenge for quantum technology researchers is to show that it offers absolute advantages over current methods.</p>
<p>Entanglement is already <a href="https://www.forbes.com/sites/forbesbusinesscouncil/2021/05/24/big-data-security-in-a-post-quantum-world/?sh=601c830a91db">used</a> by financial institutions and government agencies to communicate with guaranteed security. It is also at the heart of quantum computers, which <a href="https://www.nature.com/articles/s41586-019-1666-5">Google</a> showed in 2019 can perform calculations that would be impossible with current conventional computers.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/406899/original/file-20210617-17-1qmjsx6.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/406899/original/file-20210617-17-1qmjsx6.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/406899/original/file-20210617-17-1qmjsx6.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/406899/original/file-20210617-17-1qmjsx6.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/406899/original/file-20210617-17-1qmjsx6.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/406899/original/file-20210617-17-1qmjsx6.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/406899/original/file-20210617-17-1qmjsx6.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Lead author Dr Catxere Casacio working with the microscope in the lab.</span>
<span class="attribution"><span class="source">University of Queensland</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>Quantum sensors are the last piece of this puzzle. They are predicted to improve pretty much every aspect of how we see the world, from better navigation to better health care and medical diagnostics. </p>
<p>About a year ago quantum entanglement was installed in <a href="https://arstechnica.com/science/2020/07/ligo-is-so-sensitive-it-shudders-with-the-quantum-noise-of-light/">kilometre-scale gravitational wave observatories</a>. This allows scientists to detect massive objects further away in space. </p>
<p>Our work shows that entanglement can provide an absolute sensing advantage at more normal size scales and in widespread technologies. This could have big ramifications – not only for microscopy, but also for many other applications such as <a href="https://phys.org/news/2020-04-quantum-entanglement-unprecedented-precision-gps.html">global positioning</a>, <a href="https://www.imperial.ac.uk/be-inspired/magazine/issue-46/how-quantum-entangled-the-world/">radar and navigation</a>.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-second-quantum-revolution-is-almost-here-we-need-to-make-sure-it-benefits-the-many-not-the-few-161878">The 'second quantum revolution' is almost here. We need to make sure it benefits the many, not the few</a>
</strong>
</em>
</p>
<hr>
<img src="https://counter.theconversation.com/content/161182/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Warwick Bowen would like to acknowledge the continued support of the United States Air Force Office of Scientific Research and the ARC Centre of Excellence for Engineered Quantum Systems, without whom this research would not have been possible. He also receives funding from the Australian Research Council, Australian Defence, and the United States Army Research Office. He is a founder and director of the scientific instrumentation company Elemental Instruments.</span></em></p>Quantum microscopes reveal biological structures that would otherwise be impossible to see.Warwick Bowen, Professor of Quantum and Precision Technologies, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1581772021-04-06T12:27:48Z2021-04-06T12:27:48ZThe 17th-century cloth merchant who discovered the vast realm of tiny microbes – an appreciation of Antonie van Leeuwenhoek<figure><img src="https://images.theconversation.com/files/392870/original/file-20210331-13-1k3l5mc.jpg?ixlib=rb-1.1.0&rect=46%2C7%2C5068%2C3396&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Leeuwenhoek refined the magnifying glass, creating the world's first microscope.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/model-of-leeuwenhoek-microscope-on-book-royalty-free-image/75650913">Tetra Images via Getty Images</a></span></figcaption></figure><p>Imagine trying to cope with a pandemic like COVID-19 in a world where microscopic life was unknown. Prior to the 17th century, people were limited by what they could see with their own two eyes. But then a Dutch cloth merchant changed everything. </p>
<p>His name was Antonie van Leeuwenhoek, and he lived from 1632 to 1723. Although untrained in science, van Leeuwenhoek became the greatest lens-maker of his day, discovered microscopic life forms and is <a href="https://makingscience.royalsociety.org/s/rs/people/fst00039851">known today as the “father of microbiology.”</a></p>
<h2>Visualizing ‘animalcules’ with a ‘small see-er’</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/392877/original/file-20210331-19-kncz3z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="An oil painting of man with long curly hair holding a pair of tweezers posed next to a globe." src="https://images.theconversation.com/files/392877/original/file-20210331-19-kncz3z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/392877/original/file-20210331-19-kncz3z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=699&fit=crop&dpr=1 600w, https://images.theconversation.com/files/392877/original/file-20210331-19-kncz3z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=699&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/392877/original/file-20210331-19-kncz3z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=699&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/392877/original/file-20210331-19-kncz3z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=878&fit=crop&dpr=1 754w, https://images.theconversation.com/files/392877/original/file-20210331-19-kncz3z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=878&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/392877/original/file-20210331-19-kncz3z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=878&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Van Leeuwenhoek opened the door to a vast, previously unseen world.</span>
<span class="attribution"><a class="source" href="https://wellcomecollection.org/works/ft6mf62b">J. Verolje/Wellcome Collection</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Van Leeuwenhoek didn’t set out to identify microbes. Instead, he was trying to assess the quality of thread. He developed <a href="https://micro.magnet.fsu.edu/primer/museum/leeuwenhoek.html">a method for making lenses</a> by heating thin filaments of glass to make tiny spheres. His lenses were of such high quality he saw things no one else could.</p>
<p>This enabled him to train his microscope – literally, “small see-er” – on a new and largely unexpected realm: objects, including organisms, far too small to be seen by the naked eye. He was the <a href="https://ucmp.berkeley.edu/history/leeuwenhoek.html">first to visualize red blood cells, blood flow in capillaries and sperm</a>.</p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/392848/original/file-20210331-21-1gy6f72.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Pen and ink drawings of four different rod shaped bacteria." src="https://images.theconversation.com/files/392848/original/file-20210331-21-1gy6f72.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/392848/original/file-20210331-21-1gy6f72.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=539&fit=crop&dpr=1 600w, https://images.theconversation.com/files/392848/original/file-20210331-21-1gy6f72.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=539&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/392848/original/file-20210331-21-1gy6f72.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=539&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/392848/original/file-20210331-21-1gy6f72.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=677&fit=crop&dpr=1 754w, https://images.theconversation.com/files/392848/original/file-20210331-21-1gy6f72.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=677&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/392848/original/file-20210331-21-1gy6f72.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=677&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Drawings from a van Leeuwenhoek letter in 1683 illustrating human mouth bacteria.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Leuwenhoek_picture_of_animacules.png">Huydang2910</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>Van Leeuwenhoek was also the <a href="https://www.aaas.org/discovery-bacteria">first human being to see a bacterium</a> – and the importance of this discovery for microbiology and medicine can hardly be overstated. Yet he was reluctant to publish his findings, due to his lack of formal education. Eventually, friends prevailed upon him to do so.</p>
<p>He wrote, “Whenever I found out anything remarkable, I thought it <a href="https://ucmp.berkeley.edu/history/leeuwenhoek.html">my duty to put down my discovery on paper</a>, so that all ingenious people might be informed thereof.” He was guided by his curiosity and joy in discovery, asserting “I’ve taken no notice of those who have said <a href="https://laurieximenez.files.wordpress.com/2016/03/2-microbe-hunters-paul-de-kruif.pdf">why take so much trouble and what good is it</a>?”</p>
<p>When he reported visualizing “animalcules” (tiny animals) swimming in a drop of pond water, members of the scientific community questioned his reliability. After his findings were <a href="https://doi.org/10.1098/rsnr.2004.0055">corroborated by reliable religious and scientific authorities</a>, they were published, and in 1680 he was invited to join the Royal Society in London, then the world’s premier scientific body.</p>
<p>Van Leeuwenhoek was not the world’s only microscopist. In England, his contemporary <a href="https://theconversation.com/robert-hooke-the-english-leonardo-who-was-a-17th-century-scientific-superstar-119497">Robert Hooke coined the term “cell”</a> to describe the basic unit of life and published his “Micrographia,” featuring incredibly detailed images of insects and the like, which became the first scientific best-seller. Hooke, however, did not identify bacteria.</p>
<p>Despite van Leuwenhoek’s prowess as a lens-maker, even he could not see viruses. They are about 1/100th the size of bacteria, much too small to be visualized by light microscopes, which because of the physics of light <a href="http://www.auburn.edu/academic/classes/biol/4101/estridge2/tutorial1a.pdf">can magnify only thousands of times</a>. Viruses weren’t visualized until 1931 with the <a href="http://www.auburn.edu/academic/classes/biol/4101/estridge2/tutorial1a.pdf">invention of electron microscopes</a>, which could magnify by the millions.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/393164/original/file-20210401-17-bvjvvo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Black and white microscopic image showing a cluster of dots." src="https://images.theconversation.com/files/393164/original/file-20210401-17-bvjvvo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/393164/original/file-20210401-17-bvjvvo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=495&fit=crop&dpr=1 600w, https://images.theconversation.com/files/393164/original/file-20210401-17-bvjvvo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=495&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/393164/original/file-20210401-17-bvjvvo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=495&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/393164/original/file-20210401-17-bvjvvo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=622&fit=crop&dpr=1 754w, https://images.theconversation.com/files/393164/original/file-20210401-17-bvjvvo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=622&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/393164/original/file-20210401-17-bvjvvo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=622&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">An image of the hepatitis virus courtesy of the electron microscope.</span>
<span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/Hepatitis/20c83d41c4ef41a593761c96f6565697">E.H. Cook, Jr./CDC via Associated Press</a></span>
</figcaption>
</figure>
<h2>A vast, previously unseen world</h2>
<p>Van Leeuwenhoek and his successors opened up, by far, the largest realm of life. For example, all the bacteria on Earth <a href="https://www.vox.com/science-and-health/2018/5/29/17386112/all-life-on-earth-chart-weight-plants-animals-pnas">outweigh humans by more than 1,100 times</a> and outnumber us by an unimaginable margin. There is fossil evidence that <a href="https://ucmp.berkeley.edu/bacteria/bacteriafr.html">bacteria were among the first life forms on Earth</a>, dating back over 3 billion years, and today it is thought the planet houses about <a href="http://news.bbc.co.uk/2/hi/science/nature/158203.stm">5 nonillion (1 followed by 30 zeroes) bacteria</a>.</p>
<p>Some species of <a href="https://sphweb.bumc.bu.edu/otlt/mph-modules/ph/ph709_infectiousagents/PH709_InfectiousAgents4.html">bacteria cause diseases</a>, such as cholera, syphilis and strep throat; while <a href="https://doi.org/10.3389/fmicb.2019.00780">others, known as extremophiles</a>, can survive at temperatures beyond the boiling and freezing points of water, from the upper reaches of the atmosphere to the deepest points of the oceans. Also, the number of harmless bacterial cells on and in our bodies <a href="https://www.nature.com/news/scientists-bust-myth-that-our-bodies-have-more-bacteria-than-human-cells-1.19136">likely outnumber the human ones</a>.</p>
<p>Viruses, which include the coronavirus SARS-CoV-2 that causes COVID-19, outnumber bacteria by a factor of 100, meaning there are <a href="https://www.nationalgeographic.com/science/article/factors-allow-viruses-infect-humans-coronavirus">more of them on Earth than stars in the universe</a>. They, too, are found everywhere, from the upper atmosphere to the ocean depths.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/392874/original/file-20210331-21-1jfdfea.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A black and white image showing a segmented sphere shaped item." src="https://images.theconversation.com/files/392874/original/file-20210331-21-1jfdfea.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/392874/original/file-20210331-21-1jfdfea.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=580&fit=crop&dpr=1 600w, https://images.theconversation.com/files/392874/original/file-20210331-21-1jfdfea.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=580&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/392874/original/file-20210331-21-1jfdfea.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=580&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/392874/original/file-20210331-21-1jfdfea.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=728&fit=crop&dpr=1 754w, https://images.theconversation.com/files/392874/original/file-20210331-21-1jfdfea.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=728&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/392874/original/file-20210331-21-1jfdfea.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=728&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A visualization of the human rhinovirus 14, one of many viruses that cause the common cold. Protein spikes are colored white for clarity.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Rhinovirus_isosurface.png">Thomas Splettstoesser</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>Strangely, <a href="https://www.scientificamerican.com/article/are-viruses-alive-2004/">viruses probably do not qualify as living organisms</a>. They can replicate only by infecting other organisms’ cells, where they hijack cellular systems to make copies of themselves, sometimes causing the death of the infected cell.</p>
<p>It is important to remember that microbes such as bacteria and viruses do far more than cause disease, and many are vital to life. For example, <a href="https://doi.org/10.1177/1535370217746612">bacteria synthesize vitamin B12</a>, without which most living organisms would not be able to make DNA.</p>
<p>Likewise, viruses cause diseases such as the common cold, influenza and COVID-19, but they also play a vital role in transferring genes between species, which <a href="https://www.sciencedaily.com/releases/2016/07/160713100911.htm">helps to increase genetic diversity and propel evolution</a>. Today <a href="https://www.cancer.gov/news-events/cancer-currents-blog/2018/oncolytic-viruses-to-treat-cancer">researchers use viruses to treat diseases such as cancer</a>.</p>
<p>Scientists’ understanding of microbes has progressed a long way since van Leeuwenhoek, including the development of antibiotics against bacteria and vaccines against viruses including SARS-CoV-2. </p>
<p>But it was van Leeuwenhoek who first opened people’s eyes to life’s vast microscopic realm, a discovery that continues to transform the world.</p>
<p>[<em>Understand new developments in science, health and technology, each week.</em> <a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-understand">Subscribe to The Conversation’s science newsletter</a>.]</p><img src="https://counter.theconversation.com/content/158177/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Richard Gunderman does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Van Leeuwenhoek, who discovered bacteria, is one of the most important figures in the history of medicine, laying the groundwork for today’s understanding of infectious disease.Richard Gunderman, Chancellor's Professor of Medicine, Liberal Arts, and Philanthropy, Indiana UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1478962021-03-29T12:07:56Z2021-03-29T12:07:56Z‘Frugal design’ brings medical innovations to communities that lack resources during the pandemic<figure><img src="https://images.theconversation.com/files/391474/original/file-20210324-21-3yp66r.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C4240%2C2380&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Maker spaces give engineers and designers the tools to build low-cost medical equipment using locally available materials.</span> <span class="attribution"><span class="source">Brandon Martin, Rice University</span>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span></figcaption></figure><p>Dr. Msandeni Chiume Kayuni found herself in the middle of a supply crisis as COVID-19 spread to Africa in April 2020. As head of Pediatrics at Kamuzu Central Hospital in Lilongwe, Malawi, her team faced a critical shortage of N95 and regular surgical face masks. Nurses and doctors were striking. </p>
<p>“We had members of hospital staff put their tools down because they did not feel it was safe to practice,” she told us in an interview.</p>
<p>Ingenuity kicked in. The Malawi team purchased raincoats from the local market to use as personal protective equipment when they could not afford appropriate gowns that cost three times as much. Unlike disposable gowns, the rain gear could easily be sanitized in bleach and reused.</p>
<p>Worldwide, as the global supply chain for basic PPE, diagnostic tests and equipment to treat critically ill COVID-19 patients buckled under the strain, medical personnel improvised and engineers began developing solutions almost overnight. Engineering students used university-based maker spaces to invent and produce new technologies – face shields, automated hand washing stations, diagnostic testing equipment and respiratory support equipment – that allowed health care workers to safely deliver effective care.</p>
<p>As engineers working in the <a href="https://scholar.google.com/citations?user=JvDMZEMAAAAJ&hl=en">U.S.</a> and <a href="https://www.researchgate.net/profile/Theresa-Mkandawire">Malawi</a> to develop effective and affordable medical devices for low-resource communities, we routinely practice and teach this level of resourcefulness, dubbed “frugal design.”</p>
<h2>Spreading the light</h2>
<p>Medical personnel reused available N95 masks, intended to be used once, for weeks or months, which required innovative ways to disinfect them, including heaters, gas sterilizers and ultraviolet light.</p>
<p>UVC – short-wavelength ultraviolet light – <a href="https://theconversation.com/ultraviolet-light-can-make-indoor-spaces-safer-during-the-pandemic-if-its-used-the-right-way-141512">kills or inactivates viruses</a>, including SARS-CoV-2, the virus that causes COVID-19. In the pandemic, scientists set up UVC systems in spare rooms at hospitals to sanitize masks. </p>
<p><a href="https://www.nebraskamed.com/sites/default/files/documents/covid-19/n-95-decon-process.pdf">The University of Nebraska Medical Center</a> equipped a room with UVC light towers and coated the walls with reflective foil to maximize the dose of UVC light. Dirty masks are clipped to rows of clothesline strung across the UVC room. An operator outside the room started the lights, and a detector in the room ensured the masks had received a virus-killing dose of light. Masks can be disinfected and <a href="https://doi.org/10.1080/15459624.2015.1018518">reused multiple times</a> without damaging their integrity. </p>
<p>Engineers in Houston, Malawi and Tanzania worked together to reduce the cost of <a href="https://a35c7f44-33a6-4729-a16a-f1176754cacf.filesusr.com/ugd/0b77a5_1bd6601353084b28b6e22302082fbbda.pdf">room-based UVC disinfection systems</a> to less than US$800, and several systems are now installed in hospitals in Malawi and Tanzania. Engineers at other locations <a href="https://doi.org/10.1101/2020.04.29.20085456">built disinfecting stations</a> by adapting UV lights in the hoods normally used to grow cells in culture or by repurposing the <a href="https://hackaday.com/2020/06/16/a-properly-engineered-uv-chamber-for-ppe-sanitization/">UV light in an aquarium sanitizer</a>.</p>
<h2>Local innovation for PPE</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/391482/original/file-20210324-13-o68y9h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A woman wearing a lab coat, face mask and hair covering holds two plastic face shields" src="https://images.theconversation.com/files/391482/original/file-20210324-13-o68y9h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/391482/original/file-20210324-13-o68y9h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=1066&fit=crop&dpr=1 600w, https://images.theconversation.com/files/391482/original/file-20210324-13-o68y9h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=1066&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/391482/original/file-20210324-13-o68y9h.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=1066&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/391482/original/file-20210324-13-o68y9h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1340&fit=crop&dpr=1 754w, https://images.theconversation.com/files/391482/original/file-20210324-13-o68y9h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1340&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/391482/original/file-20210324-13-o68y9h.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1340&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Health care workers around the world turned to 3D-printed face shields in the early months of the pandemic.</span>
<span class="attribution"><span class="source">Julia Jenjezwa, Rice 360° Institute for Global Health</span>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>Across the world, engineering students used novel maker spaces at universities with 3D printers and laser cutters to rush new PPE designs into large-scale local production. Students and staff at Malawi’s two engineering schools, Malawi Polytechnic and the Malawi University of Science and Technology, and at Tanzania’s Dar es Salaam Institute of Technology, <a href="https://www.nest360.org/post/dit-design-studio-innovation-for-covid-19-preparedness-in-tanzania">adapted open-source</a> designs to produce face shields. They consulted with clinicians at partner hospitals to improve comfort and safety while using only locally available materials. </p>
<p>Development organizations, including UNICEF and the United Nations Development Program, ordered over 8,000 face shields that were locally produced and delivered to area hospitals.</p>
<h2>Rethinking diagnostics designs</h2>
<p>Diagnostic laboratories could not obtain key supplies needed to run COVID-19 tests in the early stages of the pandemic. In early 2020, major hospitals and public health systems struggled to obtain <a href="https://www.mckinsey.com/industries/pharmaceuticals-and-medical-products/our-insights/covid-19-overcoming-supply-shortages-for-diagnostic-testing">swabs, sample tubes, reagents and equipment</a> needed to meet the increased demand for testing. </p>
<p>The first available COVID-19 test relied on <a href="https://www.who.int/docs/default-source/coronaviruse/whoinhouseassays.pdf?sfvrsn=de3a76aa_2">polymerase chain reaction</a>, or PCR, a method that increases the amount of a viral RNA in a sample to detectable levels. This method of testing requires specialized reagents and equipment to isolate viral RNA, transform it to DNA, and trigger the amplification process. </p>
<p>Because of the complexity of PCR-based testing and the scarcity of test reagents, the National Institutes of Health <a href="https://doi.org/10.1056/NEJMsr2022263">invested $1.5B in the RADx program</a> to spur innovators to find novel, affordable diagnostic tests. Many innovative tests have received <a href="https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas#individual-molecular">emergency use authorization</a> from the Food and Drug Administration and are now used throughout the world.</p>
<p>For example, <a href="https://doi.org/10.1073/pnas.2011221117">researchers at Harvard</a> used a simple single-temperature reaction to amplify viral RNA, eliminating many of the necessary steps and reagents of PCR and speeding up the testing time. Researchers at Stanford adapted the <a href="https://twitter.com/i/status/1279182764781088768">mechanism inside a toy flashlight</a> to build a <a href="https://www.chemistryworld.com/news/hand-powered-centrifuge-setup-can-diagnose-covid-19-for-just-a-dollar-a-test/4012142.article">simple electricity-free centrifuge</a> to help perform this new COVID-19 test in areas that lack electricity and other laboratory infrastructure.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/uqiPNUp8hvs?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Devices like this hand-powered centrifuge could make COVID-19 testing more accessible in communities with limited access to electricity.</span></figcaption>
</figure>
<h2>Reinforcing ventilator supplies</h2>
<p>In response to the global shortage of ventilators in the first months of the pandemic last year, engineers designed simple devices to provide temporary breathing support. Open-source plans for two systems, <a href="https://doi.org/10.1007/s00134-020-06113-3">one</a> designed by the <a href="https://emergency-vent.mit.edu/">MIT Emergency Ventilator Project</a> and one designed by students and staff at <a href="http://oedk.rice.edu/apollobvm/">Rice University</a>, are available online. </p>
<p>A global <a href="https://www.cidrap.umn.edu/news-perspective/2021/03/who-sounds-alarm-over-covid-linked-oxygen-crisis">shortage of oxygen</a> in low-resource countries has led many health care providers in those countries to fall back on mechanical ventilation. Ventilators are also in short supply, in part because of <a href="https://www.washingtonpost.com/national-security/2021/01/29/usaid-trump-ventilators-watchdog/">problems with a U.S. ventilator donation program</a>.</p>
<p>Students and faculty at the Malawi University of Science and Technology developed a <a href="https://www.nest360.org/post/malawi-design-studios-poly-must-provide-locally-sourced-ppe-technologies-to-respond-to-covid-19">system similar to the MIT and Rice ventilators</a> that can be assembled using materials available in Malawi. Students at Malawi Polytechnic worked with local physicians to <a href="https://www.iol.co.za/news/africa/young-engineers-offer-new-hope-for-malawi-in-covid-19-fight-47086599">develop a ventilator with more features</a>.</p>
<h2>Hygiene innovation</h2>
<p>Public health officials emphasize the role of <a href="https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public">hand-washing, together with social distancing and face masks</a>, to curb the continued spread of COVID-19. However, many schools and even some hospitals in low-resource settings do not have running water and sinks allowing students and patients to regularly wash their hands. </p>
<p>In response, Brenald Dzonzi, an engineering student at Malawi Polytechnic, designed a no-touch hand-washing station. Small amounts of soap and water are automatically dispensed from pre-filled containers when a user stands in front of the station. The system is made from local materials and is now installed at a local hospital. Up to 2,000 patients can safely wash their hands before the system needs to be refilled. </p>
<p>Dzonzi was awarded the <a href="https://www.unicef.org/malawi/stories/brenald-touch-free-disinfection-public-places">UNICEF Youth Challenge award</a> to fund continued development of the hand-washing station.</p>
<h2>Elegant and sustainable design</h2>
<p>When equipment is unsuitable for an environment, because it can’t tolerate hot, dusty conditions, for example, it ends up discarded in equipment graveyards — serving no one. In contrast, successfully executed <a href="https://doi.org/10.1126/science.1257085">frugal designs</a> offer sustainability and suitability for low-resource environments. </p>
<figure class="align-center ">
<img alt="numerous rows of medical equipment in a storeroom" src="https://images.theconversation.com/files/366808/original/file-20201030-14-1abkwp6.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/366808/original/file-20201030-14-1abkwp6.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=281&fit=crop&dpr=1 600w, https://images.theconversation.com/files/366808/original/file-20201030-14-1abkwp6.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=281&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/366808/original/file-20201030-14-1abkwp6.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=281&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/366808/original/file-20201030-14-1abkwp6.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=353&fit=crop&dpr=1 754w, https://images.theconversation.com/files/366808/original/file-20201030-14-1abkwp6.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=353&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/366808/original/file-20201030-14-1abkwp6.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=353&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A medical equipment ‘graveyard’ in Malawi.</span>
<span class="attribution"><span class="source">Rice 360° Institute for Global Health</span>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>An example of this type of elegant design is the <a href="https://doi.org/10.1371/journal.pone.0098781">FoldScope</a>, a low-cost paper microscope used to improve medical diagnostics and science education in low-resource settings. Other examples include <a href="https://equalizehealth.org/products/brilliance">LED-based</a> phototherapy lights used to treat jaundice in newborns, and <a href="https://doi.org/10.1371/journal.pone.0235031">low-cost CPAPs</a> that bring breathing support to small and sick newborns in low-resource health care facilities.</p>
<p>To encourage frugal design, universities across the world are changing <a href="https://doi.org/10.1126/science.1213947">how they teach engineering</a> — focusing on frugal design and engaging students like Dzonzi to invent solutions that <a href="https://doi.org/10.1007/s10439-016-1777-1">solve real problems</a>. Though the pandemic sparked a global need for frugal design, the practice is important generally for narrowing the health care gap between high- and low-resource communities and bringing health care services to underserved communities.</p><img src="https://counter.theconversation.com/content/147896/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rebecca Richards-Kortum receives funding from the National Institutes of Health, the National Science Foundation, the Bill & Melinda Gates Foundation, the MacArthur Foundation, ELMA Philanthropies, the Children's Investment Fund Foundation, and the Lemelson Foundation. </span></em></p><p class="fine-print"><em><span>Theresa Mkandawire does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Engineering students in Malawi and Tanzania have used the materials and tools available to them to build ventilators, personal protective equipment and UV disinfection systems.Rebecca Richards-Kortum, Professor of Bioengineering, Rice UniversityTheresa Mkandawire, Associate Professor of Civil Engineering, University of MalawiLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1567192021-03-23T16:36:17Z2021-03-23T16:36:17ZCancer: tiny diamonds in cells could help to understand development process<figure><img src="https://images.theconversation.com/files/390933/original/file-20210322-13-1l38eav.jpg?ixlib=rb-1.1.0&rect=0%2C13%2C4500%2C4479&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-rendered-medically-accurate-illustration-human-1061676194">SciePro/Shutterstock</a></span></figcaption></figure><p>Over the years, scientists have put together an amazing array of microscopic markers that they can place within cells whenever they need to label and observe distinct parts of a cell’s interior. Such labelling is used for a wide array of research, including cancer research.</p>
<p>But sneaking these markers into cells, through the membrane that protects them from unwanted substances, is far from easy. Creating too wide a breach in the cell membrane when injecting the markers can be fatal for the cell. Plus, once they’re smuggled inside, many markers are actually toxic – and are either attacked by the cell, or lead to its demise.</p>
<p>In the search for non-toxic markers, scientists have landed upon nanodiamonds: identical to those bejewelling engagement rings, but a million times smaller. Nanodiamonds make excellent reporters within cells, but they’re yet to feature in scientists’ toolkits because getting them inside the cell without damaging the membrane has proven too difficult.</p>
<p>Led by my supervisor Christelle Prinz from NanoLund, Lund University, our team has created a new way to sneak nanodiamonds into cells without causing damage or provoking the cell to attack them. <a href="https://onlinelibrary.wiley.com/doi/full/10.1002/smll.202006421">Our new technique</a> will help scientists study the properties of living cells at the molecular level, but it could also become a versatile new tool to help us understand more about cellular diseases like cancer and Alzheimer’s.</p>
<h2>Monitoring cells</h2>
<p>Our bodies are built out of approximately <a href="https://www.tandfonline.com/doi/abs/10.3109/03014460.2013.807878?journalCode=iahb20">40 trillion cells</a>, ranging between 1 and 100 micrometers in size. Some of these cells sometimes get sick – causing cancer in various tissues, or neurological diseases such as Alzheimer’s in brain cells. By monitoring sick cells, researchers can learn more about the origins and development of these diseases.</p>
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<strong>
Read more:
<a href="https://theconversation.com/cancer-growth-in-the-body-could-originate-from-a-single-cell-target-it-to-revolutionise-treatment-110921">Cancer growth in the body could originate from a single cell – target it to revolutionise treatment</a>
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<p>Microscopes can peek within a cell, but they’re poor at discerning a diseased cell from its healthy counterpart. For more detailed monitoring, researchers label cells with biological markers which expose more about what’s happening inside cells.</p>
<p>Existing biological markers, like organic dyes and fluorescent proteins, can expose some of the conditions within a cell for researchers to study. But these markers often kill the cell, limiting their utility for long-term cellular studies. Nanodiamonds, on the other hand, don’t kill cells – which is why they’re now being used by researchers in <a href="https://aip.scitation.org/doi/abs/10.1063/1.4922557">cellular science</a>.</p>
<h2>Why nanodiamonds?</h2>
<p><a href="https://envirodiamond.net/what-are-nano-diamonds/">Nanodiamonds</a> are either produced by detonating synthetic diamonds, or from the powder left over after milling natural diamonds. Despite their luxury connotations, they’re actually relatively cheap for researchers like us to purchase – costing about the same as existing biomarkers.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/390931/original/file-20210322-19-11tv5ml.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A group of white shards pictured against a black background" src="https://images.theconversation.com/files/390931/original/file-20210322-19-11tv5ml.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/390931/original/file-20210322-19-11tv5ml.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/390931/original/file-20210322-19-11tv5ml.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/390931/original/file-20210322-19-11tv5ml.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/390931/original/file-20210322-19-11tv5ml.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/390931/original/file-20210322-19-11tv5ml.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/390931/original/file-20210322-19-11tv5ml.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Nanodiamonds viewed by a scanning electron microscope.</span>
<span class="attribution"><span class="source">Diogo Volpati, Lund University</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>Crucially, nanodiamonds are biocompatible: they’re completely harmless and non-toxic when placed inside living tissue. That means they can lurk incognito within our cells. Once inside, nanodiamonds shine within cells – sending information back to researchers in the form of fluorescent light, the wavelength of which changes depending on the pH or the temperature within the cell.</p>
<h2>Infiltrating a cell</h2>
<p>It’s not easy getting nanodiamonds into a cell. Cell membranes have evolved an impressive protective apparatus to keep unwanted intruders outside. To sneak nanodiamonds in, we either have to hope that cells will invite them in voluntarily – a very slow and inefficient process – or else we have to force their entry through the cellular membrane.</p>
<p><a href="https://pubs.rsc.org/en/content/articlehtml/2010/jm/c0jm01570a?casa_token=kmFPx5frS5gAAAAA:ENqV4Axcy5s0AFKf-x_nLX42E2ebyV-lzu4XyMs2QwlUX4t3RtXdxg_JRutiYfGYSimpVhae9zPHBH4">Microinjection</a>, using microscopic needles, has been used to deliver markers like nanodiamonds across the cell membrane without fatally damaging the cell, but it’s a painstaking method that’s often unsuccessful.</p>
<p>Even after a successful infiltration, nanodiamonds risk being gobbled up by a cell’s lysosomes, which are a bit like a cell’s bodyguards. Biomarkers captured and confined within lysosomes are of little use for researchers trying to observe the whole cell. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/390940/original/file-20210322-17-ryhygq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A 3D diagram mapping out the anatomy of a call" src="https://images.theconversation.com/files/390940/original/file-20210322-17-ryhygq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/390940/original/file-20210322-17-ryhygq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=452&fit=crop&dpr=1 600w, https://images.theconversation.com/files/390940/original/file-20210322-17-ryhygq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=452&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/390940/original/file-20210322-17-ryhygq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=452&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/390940/original/file-20210322-17-ryhygq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=568&fit=crop&dpr=1 754w, https://images.theconversation.com/files/390940/original/file-20210322-17-ryhygq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=568&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/390940/original/file-20210322-17-ryhygq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=568&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A cell’s lysosomes, coloured orange in this diagram, tend to capture foreign agents they detect in the cell.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/human-animal-cell-cross-section-structure-213232894">Designua/Shutterstock</a></span>
</figcaption>
</figure>
<h2>Nanodiamond smugglers</h2>
<p>We’ve developed a new method to sneak large numbers of nanodiamonds into cells, largely undetected by the lysosomes, and without damaging the cell itself. Our approach combines a very gentle electric field, which eases the cell membrane open, with so-called “<a href="https://www.pnas.org/content/117/35/21267?elqTrackId=dce04abc63ab48bc9df1eea8d7f6b71d">nanostraws</a>” – like drinking straws, but nanoscopically small.</p>
<p>In <a href="https://onlinelibrary.wiley.com/doi/full/10.1002/smll.202006421">our study</a>, we used cells derived from a patient with lung cancer. We lay these cells on thousands of nanostraws, comparable to a minuscule bed of nails. Underneath these nanostraws lay our nanodiamonds, in a slightly conductive solution.</p>
<p>When we applied low-voltage electrical pulses to the nanostraws, small openings appeared across the cellular membrane, at the tip of each nanostraw, creating an access pathway for the nanodiamonds to reach the cell’s interior. </p>
<p>The electric pulses encouraged the conductive solution to travel up through the straws, dragging the nanodiamonds with it through the tiny breaches in the cell membrane. When we stopped the pulses, the small openings in the cell membrane closed behind the smuggled cargo of nanodiamonds.</p>
<h2>A cell’s best friend</h2>
<p>Our new technique is roughly 300 times quicker than simply incubating cells in a solution of nanodiamonds and waiting for some of them to naturally pass into the cell. It also halved the entrapment of nanodiamonds inside lysosomes, thus allowing a big portion of the delivered nanodiamonds to stay free and mobile inside the cell’s interior: a successful infiltration. </p>
<p>Because nanodiamonds can report on the temperature or acidity of different parts of a cell over time, we hope our nanodiamond infiltration technique could help <a href="https://doi.org/10.1186/s12951%E2%80%91018%E2%80%910385%E2%80%917">identify and track</a> cancer cells, or brain cells that are implicated with Alzheimer’s disease. And, if we can find a way to pair nanodiamonds with certain chemicals, we could also find even more refined ways to spy on conditions within the fundamental building blocks of our bodies.</p><img src="https://counter.theconversation.com/content/156719/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span><a href="mailto:elke.hebisch@ftf.lth.se">elke.hebisch@ftf.lth.se</a> receives funding from a seedling project grant through NanoLund; for the research study, my supervisor <a href="mailto:christelle.prinz@ftf.lth.se">christelle.prinz@ftf.lth.se</a> receives funding from the ERC-CoG grant NanoPokers (662206); the Swedish Foundation for Strategic Research (ITM17 grant), the Swedish Research Council, the Crafoord Foundation, and NanoLund. Also it is to be mentioned that one of our co-authors (Martin Hjort) is Chief Technology Officer at Navan Technologies, Inc., a startup commercializing nanostraws.</span></em></p>Nanodiamonds aren’t just cellular bling: they could be used to better understand the development of cancer in our cells.Elke Hebisch, Researcher, Department of Solid State Physics, Lund UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1343802020-03-30T19:08:43Z2020-03-30T19:08:43ZScary red or icky green? We can’t say what colour coronavirus is and dressing it up might feed fears<figure><img src="https://images.theconversation.com/files/322517/original/file-20200324-155695-1kaxgif.jpg?ixlib=rb-1.1.0&rect=20%2C20%2C4452%2C2775&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://image.shutterstock.com/image-illustration/coronavirus-covid19-group-molecules-bacteria-600w-1680340612.jpg">Shutterstock</a></span></figcaption></figure><p>Images of the latest coronavirus have become instantly recognisable, often vibrantly coloured and floating in an opaque background. In most representations, the shape of the virus is the same – a spherical particle with spikes, resembling an alien invader. </p>
<p>But there’s little consensus about the colour: images of the virus come in red, orange, blue, yellow, steely or soft green, white with red spikes, red with blue spikes and many colours in between. </p>
<p>In their depictions of the virus, designers, illustrators and communicators are making some highly creative and evocative decisions.</p>
<h2>Colour, light and fear</h2>
<p>For some, the lack of consensus about the appearance of viruses confirms fears and <a href="https://www.cjc-online.ca/index.php/journal/article/view/2738/2481">increases anxiety</a>. On March 8 2020, the director-general of the World Health Organisation <a href="https://www.who.int/dg/speeches/detail/director-general-s-remarks-at-the-media-briefing-on-2019-novel-coronavirus---8-february-2020">warned</a> of the “infodemic” of misinformation about the coronavirus, urging communicators to use “facts not fear” to battle the flood of rumours and myths. </p>
<p>The confusion about the colour of coronavirus starts with the failure to understand the nature of colour in the sub-microscopic world. </p>
<p>Our <a href="https://www.pantone.com/color-intelligence/articles/technical/how-do-we-see-color">perception of colour</a> is dependent on the presence of light. White light from the sun is a combination of all the wavelengths of visible light – from violet at one end of the spectrum to red at the other. </p>
<p>When white light hits an object, we see its colour thanks to the light that is reflected by that object towards our eyes. Raspberries and rubies appear red because they absorb most light but reflect the red wavelength. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/323865/original/file-20200330-146699-1526z4d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/323865/original/file-20200330-146699-1526z4d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/323865/original/file-20200330-146699-1526z4d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/323865/original/file-20200330-146699-1526z4d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/323865/original/file-20200330-146699-1526z4d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/323865/original/file-20200330-146699-1526z4d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/323865/original/file-20200330-146699-1526z4d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/323865/original/file-20200330-146699-1526z4d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">An artist’s impression of the pandemic virus.</span>
<span class="attribution"><a class="source" href="https://images.unsplash.com/photo-1584036561566-baf8f5f1b144?ixlib=rb-1.2.1&auto=format&fit=crop&w=889&q=80">Fusion Medical Animation/Unsplash</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>But as objects become smaller, light is no longer an effective tool for seeing. Viruses are so small that, until the 1930s, one of their scientifically recognised properties was their <a href="https://link.springer.com/article/10.1007/s10739-018-9530-2">invisibility</a>. Looking for them with a microscope using light is like trying to find an ant in a football stadium at night using a large searchlight: the scale difference between object and tool is too great. </p>
<p>It wasn’t until the development of the electron microscope in the 1930s that researchers could “see” a virus. By using electrons, which are vastly smaller than light particles, it became possible to identify the shapes, structures and textures of viruses. But as no light is involved in this form of seeing, there is no colour. Images of viruses reveal a monochrome world of grey. Like electrons, atoms and quarks, viruses exist in a realm where colour has no meaning.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/323866/original/file-20200330-146724-1k76ldz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/323866/original/file-20200330-146724-1k76ldz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/323866/original/file-20200330-146724-1k76ldz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/323866/original/file-20200330-146724-1k76ldz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/323866/original/file-20200330-146724-1k76ldz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/323866/original/file-20200330-146724-1k76ldz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/323866/original/file-20200330-146724-1k76ldz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/323866/original/file-20200330-146724-1k76ldz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A colorised scanning electron micrograph image of a VERO E6 cell (blue) heavily infected with SARS-COV-2 virus particles (orange), isolated from a patient sample.</span>
<span class="attribution"><a class="source" href="https://flic.kr/p/2iG5Xsm">NIAID/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>Vivid imagery</h2>
<p>Grey images of unfamiliar blobs don’t make for persuasive or emotive media content. </p>
<p>Research into the representation of the Ebola virus outbreak in 1995 <a href="https://journals.sagepub.com/doi/abs/10.1177/0392192107087919">revealed</a> the image of choice was not the worm-like virus but teams of Western medical experts working in African villages in hermetically sealed suits. The early visual representation of the AIDS virus focused on the emaciated bodies of those with the resulting disease, often younger men. </p>
<p>With symptoms similar to the common cold and initial death rates highest amongst the elderly, the coronavirus pandemic provides no such dramatic visual material. To fill this void, the vivid range of colourful images of the coronavirus have strong appeal.</p>
<p>Many images come from stock photo suppliers, typically photorealistic artists’ impressions rather than images from electron microscopes. </p>
<p>The Public Health Library of the US government’s Centre for Disease Control (CDC) provides one such illustration, created to reveal the morphology of the coronavirus. It’s an off-white sphere with yellow protein particles attached and red spikes emerging from the surface, creating the distinctive “corona” or crown. All of these colour choices are creative decisions. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/323862/original/file-20200330-146678-1vqfors.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/323862/original/file-20200330-146678-1vqfors.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/323862/original/file-20200330-146678-1vqfors.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=336&fit=crop&dpr=1 600w, https://images.theconversation.com/files/323862/original/file-20200330-146678-1vqfors.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=336&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/323862/original/file-20200330-146678-1vqfors.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=336&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/323862/original/file-20200330-146678-1vqfors.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=423&fit=crop&dpr=1 754w, https://images.theconversation.com/files/323862/original/file-20200330-146678-1vqfors.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=423&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/323862/original/file-20200330-146678-1vqfors.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=423&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The CDC illustration reveals ‘ultrastructural morphology’ exhibited by coronaviruses.</span>
<span class="attribution"><a class="source" href="https://phil.cdc.gov/Details.aspx?pid=23311">CDC/Alissa Eckert, MS; Dan Higgins/MAMS</a></span>
</figcaption>
</figure>
<p>Biologist David Goodsell takes artistic interpretation a step further, using watercolour <a href="https://pdb101.rcsb.org/sci-art/goodsell-gallery/coronavirus">painting</a> to depict viruses at the cellular level.</p>
<p>One of the complicating challenges for virus visualisation is the emergence of so-called “colour” images from electron microscopes. Using a methodology that was originally described as “<a href="https://www.sciencedirect.com/science/article/pii/S2451945616303579">painting</a>,” scientists are able to add colour to structures in the grey-scale world of imaging to help distinguish the details of cellular micro-architecture. Yet even here, the choice of colour is arbitrary, as shown in a number of coloured images of the coronavirus made available on Flickr by the National Institute of Allergy and Infectious Diseases (NIAID). In these, the virus has been variously coloured yellow, orange, magenta and blue.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/323776/original/file-20200329-146719-66091w.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/323776/original/file-20200329-146719-66091w.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/323776/original/file-20200329-146719-66091w.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=337&fit=crop&dpr=1 600w, https://images.theconversation.com/files/323776/original/file-20200329-146719-66091w.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=337&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/323776/original/file-20200329-146719-66091w.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=337&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/323776/original/file-20200329-146719-66091w.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/323776/original/file-20200329-146719-66091w.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/323776/original/file-20200329-146719-66091w.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A composite of images created by NIAID. Colours have been attributed by scientists but these are arbitrary.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/niaid/49645120251/in/album-72157712914621487/">NIAID/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>Embracing grey</h2>
<p>Whilst these images look aesthetically striking, the arbitrary nature of their colouring does little to solve WHO’s concerns about the insecurity that comes with unclear facts about viruses and disease. </p>
<p>One solution would be to embrace the colourless sub-microscopic world that viruses inhabit and accept their greyness. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/322519/original/file-20200324-155640-jtjh3z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/322519/original/file-20200324-155640-jtjh3z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/322519/original/file-20200324-155640-jtjh3z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=367&fit=crop&dpr=1 600w, https://images.theconversation.com/files/322519/original/file-20200324-155640-jtjh3z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=367&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/322519/original/file-20200324-155640-jtjh3z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=367&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/322519/original/file-20200324-155640-jtjh3z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=461&fit=crop&dpr=1 754w, https://images.theconversation.com/files/322519/original/file-20200324-155640-jtjh3z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=461&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/322519/original/file-20200324-155640-jtjh3z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=461&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Some artists’ impressions include blood platelet images.</span>
<span class="attribution"><a class="source" href="https://image.shutterstock.com/image-photo/coronavirus-2019ncov-novel-concept-resposible-600w-1625951248.jpg">Shutterstock</a></span>
</figcaption>
</figure>
<p>This has some distinct advantages: firstly, it fits the science that colour can’t be attributed where light doesn’t reach. Secondly, it renders images of the virus less threatening: without their red spikes or green bodies they seem less like hostile invaders from a science fiction fantasy. And the idea of greyness also fits the scientific notion that viruses are suspended somewhere between the <a href="https://theconversation.com/are-viruses-alive-giant-discovery-suggests-theyre-more-like-zombies-75661">dead and the living</a>. </p>
<p>Stripping the coronavirus of the distracting vibrancy of vivid colour – and seeing it consistently as an inert grey particle – could help reduce community fear and better allow us to continue the enormous collective task of managing its biological and social impact.</p><img src="https://counter.theconversation.com/content/134380/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Simon Weaving does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Viruses exist in a realm where there is no light and colour has no meaning. In their COVID-19 depictions, designers, illustrators and communicators make some highly creative and evocative decisions.Simon Weaving, Senior Lecturer, School of Creative Industries, University of NewcastleLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1194972019-07-17T15:50:12Z2019-07-17T15:50:12ZRobert Hooke: The ‘English Leonardo’ who was a 17th-century scientific superstar<figure><img src="https://images.theconversation.com/files/284403/original/file-20190716-173360-1snh4g3.JPG?ixlib=rb-1.1.0&rect=0%2C337%2C1359%2C1133&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">No contemporary portrait of Robert Hooke seems to have survived. This 2004 oil painting is based on descriptions during his lifetime.</span> <span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:13_Portrait_of_Robert_Hooke.JPG">Rita Greer</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>Considering his accomplishments, it’s a surprise that Robert Hooke isn’t more renowned. As a physician, I especially esteem him as the person who identified biology’s most essential unit, the cell. </p>
<p>Like <a href="https://theconversation.com/8-things-you-may-not-know-about-leonardo-da-vinci-on-the-500th-anniversary-of-his-death-109318">Leonardo da Vinci</a>, Hooke excelled in an incredible array of fields. The remarkable range of his achievements throughout the 1600s encompassed pneumatics, microscopy, mechanics, astronomy and even civil engineering and architecture. Yet this “<a href="http://www.roberthooke.org.uk/leonardo.htm">English Leonardo</a>” – well-known in his time – <a href="https://www.jstor.org/stable/1293463">slipped into relative obscurity</a> for several centuries.</p>
<h2>His life and times</h2>
<p><a href="https://www.famousscientists.org/robert-hooke/">Hooke’s life</a> is a rags-to-riches tale. Born in 1635, he was educated at home by his clergyman father. Orphaned at 13 with a meager inheritance, Hooke’s artistic talents landed him scholarships to Westminster School and later Oxford University. There he formed relationships with a variety of important people, most notably <a href="https://www.famousscientists.org/robert-boyle/">Robert Boyle</a>. Hooke became the laboratory assistant of this great chemist – the formulator of Boyle’s law, which describes the inverse relation between the pressure and volume of gases.</p>
<p>Unlike his associates, Hooke was not a man of independent means, and he soon took a paying position as “curator of experiments” at the newly formed <a href="https://makingscience.royalsociety.org/s/rs/people/fst00009590">Royal Society</a>, making him England’s first salaried scientific researcher. Hooke soon became a fellow of the Royal Society and was appointed to a professorship at Gresham College.</p>
<p>Never marrying, he dwelt the rest of his life in rooms near the Royal Society’s meeting place. This placed him at the epicenter of one of the most important epochs in the history of science, epitomized by the publication of Isaac Newton’s “<a href="https://cudl.lib.cam.ac.uk/view/PR-ADV-B-00039-00001">Mathematical Principles of Natural Philosophy</a>.”</p>
<h2>Experiments and innovations</h2>
<p>For millennia before Hooke, people had regarded air, along with fire, water and earth, as one of the four elemental substances that filled the world, leaving no empty spaces. Working with Boyle, Hooke developed a <a href="https://www.ncbi.nlm.nih.gov/pubmed/16909884">vacuum pump</a> that could empty space. In a vessel so evacuated, a candle couldn’t burn, and a clapping bell was silent, proving that air is necessary for combustion and conducting sound.</p>
<p>Moreover, Hooke showed that air could be expanded and compressed. He also performed foundational experiments on the relationship between air and the process of respiration in living organisms. And he laid the groundwork for thermodynamics, by suggesting that particles in matter move faster as they heat up.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/284401/original/file-20190716-173351-60y9r9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/284401/original/file-20190716-173351-60y9r9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/284401/original/file-20190716-173351-60y9r9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=878&fit=crop&dpr=1 600w, https://images.theconversation.com/files/284401/original/file-20190716-173351-60y9r9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=878&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/284401/original/file-20190716-173351-60y9r9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=878&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/284401/original/file-20190716-173351-60y9r9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1103&fit=crop&dpr=1 754w, https://images.theconversation.com/files/284401/original/file-20190716-173351-60y9r9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1103&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/284401/original/file-20190716-173351-60y9r9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1103&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A page from ‘Micrographia’ illustrating the tiny cells of cork Hooke saw under the microscope.</span>
<span class="attribution"><a class="source" href="https://wellcomecollection.org/works/jcm8kb66?wellcomeImagesUrl=/indexplus/image/M0010579.html">Wellcome Collection</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Hooke’s most famous work is his beautifully illustrated “<a href="https://www.bl.uk/collection-items/micrographia-by-robert-hooke-1665">Micrographia</a>,” published in 1665. The microscope had been invented 30 years before his birth. Hooke vaulted the technology forward, using an oil lamp as a light source and a water lens to focus its beams in order to enhance visualization.</p>
<p>He showed that the realm of the very small is as rich and complex and the one that meets the naked eye. Inspecting the structure of cork through his instrument, he named the units he saw cells, after the rooms of monks. Biologists now know that a human body contains approximately <a href="https://www.smithsonianmag.com/smart-news/there-are-372-trillion-cells-in-your-body-4941473/">40 trillion</a> of them. From his microscope work, Hooke also developed a wave theory of light.</p>
<p>Hooke pondered some of the biggest biological questions as well. He hypothesized that the presence of fossilized fish in mountainous areas meant they had once been under water. His study of fossils led him to conclude that the Earth has been inhabited by many extinct species.</p>
<p>Hooke’s experiments with mechanical springs led to the formulation of <a href="https://phys.org/news/2015-02-law.html">Hooke’s Law</a>, which states that the tension or compression of a spring is proportional to the force applied to it. Physicists now know that this law applies not only to springs but also to a variety of solid elastic bodies, such as manometers, which are used to measure pressure.</p>
<p>These same investigations also enabled him to invent the <a href="http://shipseducation.net/modules/phys/hooke/hooke.htm">spring-powered balance watch</a>, which would become a favorite means of keeping time for centuries. Hooke foresaw that with a precise timepiece, oceangoing sailors could find their longitude.</p>
<p><a href="http://adsabs.harvard.edu/full/1951PA%2E%2E%2E%2E%2E59%2E%2E287A">As an astronomer</a>, Hooke suggested that the planet Jupiter rotates, described the center of gravity of the Earth and Moon, illustrated lunar craters and speculated on their origin, discovered a double star and illustrated the Pleiades star cluster.</p>
<p>At a more theoretical level, Hooke also described gravity as the force that pulls celestial bodies together, relating in a <a href="https://www.newhistorian.com/2016/08/22/robert-hooke-wrath-isaac-newton/">1679 letter to Newton</a> a version of the inverse-square law of gravitational force. When seven years later Newton published his great work “Mathematical Principles,” Hooke concluded incorrectly that Newton – who had already been at work on it at the time of their correspondence – had slighted him.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/284523/original/file-20190717-147299-d05gxv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/284523/original/file-20190717-147299-d05gxv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/284523/original/file-20190717-147299-d05gxv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=414&fit=crop&dpr=1 600w, https://images.theconversation.com/files/284523/original/file-20190717-147299-d05gxv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=414&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/284523/original/file-20190717-147299-d05gxv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=414&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/284523/original/file-20190717-147299-d05gxv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=520&fit=crop&dpr=1 754w, https://images.theconversation.com/files/284523/original/file-20190717-147299-d05gxv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=520&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/284523/original/file-20190717-147299-d05gxv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=520&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Hooke and Wren’s monument to the great fire in 1666 still stands in London today.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/monument-great-fire-london-1076149199?studio=1">maziarz/Shutterstock.com</a></span>
</figcaption>
</figure>
<h2>Contributions to his city</h2>
<p>The great fire of London in 1666 presented another opportunity for Hooke to shine. Unlike many contemporaries, he refused to profit dishonestly in the aftermath of the disaster by taking bribes as people worked to rebuild. As <a href="https://doi.org/10.1098/rsnr.1997.0014">surveyor of the city</a>, he collaborated with the renowned architect Christopher Wren to <a href="https://doi.org/10.1098/rsnr.2010.0092">create a monument to the fire</a>.</p>
<p>He also <a href="https://doi.org/10.1098/rsnr.1948.0006">designed a number of great buildings</a>, including Bethlem Hospital (known as Bedlam), the Royal Greenwich Observatory and the Royal College of Physicians. It was in large part through his architectural work that Hooke made his fortune, though he never veered from the frugal habits he developed early in life. Hooke even proposed recreating London’s streets on a grid pattern. Though unsuccessful, his idea was subsequently incorporated in cities such as Liverpool and Washington, D.C.</p>
<p>Surveying the range and depth of Hooke’s contributions, it’s difficult to believe that one person could have accomplished so much in 67 years. Unfortunately, his sometimes rancorous disputes <a href="http://www.newtonproject.ox.ac.uk/view/texts/normalized/THEM00175">with the likes of Newton</a> over scientific priority contributed to his comparative neglect by <a href="https://www.jstor.org/stable/1293463?seq=1#page_scan_tab_contents">science historians</a>, and today we lack any contemporary likeness of him. His birthday is a good time to give him his due as one of the world’s all-time great instrument makers, experimentalists and polymaths.</p>
<p>[ <em>Deep knowledge, daily.</em> <a href="https://theconversation.com/us/newsletters?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=deepknowledge">Sign up for The Conversation’s newsletter</a>. ]</p><img src="https://counter.theconversation.com/content/119497/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Richard Gunderman does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Born on July 18, 1635, this polymath broke ground in fields ranging from pneumatics, microscopy, mechanics and astronomy to civil engineering and architecture.Richard Gunderman, Chancellor's Professor of Medicine, Liberal Arts, and Philanthropy, Indiana UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1039442018-10-04T09:58:07Z2018-10-04T09:58:07ZHow capitalism ruined our relationship with bacteria<figure><img src="https://images.theconversation.com/files/239101/original/file-20181003-52674-19i687t.jpg?ixlib=rb-1.1.0&rect=122%2C729%2C2446%2C1741&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://wellcomecollection.org/works/w43evtsm?query=microbes">Wellcome Collection</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>There are many rational reasons that motivate consumers to spend <a href="https://www.technavio.com/report/global-household-cleaning-products-market-analysis-share-2018?utm_source=t9&utm_medium=bw_wk31&utm_campaign=businesswire">US$65 billion</a> annually on household cleaning products. But non-rational mechanisms are nevertheless still at work in the cleaning products market, as in all others. </p>
<p>Advertisements for domestic hygiene products usually follow the same simple yet powerful structure: the threat of bacterial contamination looms large, but anti-bacterial gels, soaps, fluids, powders or foams can offer protection against it. We are encouraged to think of bacteria as entities that threaten our secluded, sovereign cleanliness. This has led us to a limited, and dangerous relationship with bacteria.</p>
<p>Consider how bacteria is portrayed visually. Although it is possible to take photographs of bacteria – and there are <a href="https://commons.wikimedia.org/wiki/Category:Microscopic_images_of_bacteria">some great pictures</a> out there – these images are generally found only in scientific and medical contexts. For the rest of us, bacteria do not appear in a realist way. Instead, they come to us through the filter of advertisements for antibacterial products.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/239097/original/file-20181003-52663-ctu79i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/239097/original/file-20181003-52663-ctu79i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=384&fit=crop&dpr=1 600w, https://images.theconversation.com/files/239097/original/file-20181003-52663-ctu79i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=384&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/239097/original/file-20181003-52663-ctu79i.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=384&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/239097/original/file-20181003-52663-ctu79i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=483&fit=crop&dpr=1 754w, https://images.theconversation.com/files/239097/original/file-20181003-52663-ctu79i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=483&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/239097/original/file-20181003-52663-ctu79i.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=483&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Airborne microbes.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Bacteria_(251_31)_Airborne_microbes.jpg">Josef Reischig, CSc/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>And it’s quite a filter. <a href="http://journals.sagepub.com/doi/full/10.1177/1470593118796678">Our analysis</a> of advertising images of bacteria from 1848 to the present day finds four broad conventions. Understanding these conventions shows how our relationship with this essential dimension of earth’s biome is subject to the aims and desires of the manufacturers of cleaning products.</p>
<h2>1. Cute bacteria</h2>
<p>First, bacteria are <a href="http://catalogue.wellcomelibrary.org/record=b1164289">cute</a>. They are <a href="https://www.coloribus.com/adsarchive/promo/multan-bacteria-have-to-stay-outside-15829105/">small, vulnerable and toy-like</a>. Their eyes are big and their limbs are tiny. This is strange, considering that advertisements for bacterial products are persuading us to kill these beings by the billion. </p>
<p>But cuteness can have a strange effect on the viewer. Sure, we want to touch, hold and even protect the thing that is cute, like a soft toy. But the cute object evinces a range of <a href="https://www.nytimes.com/2006/01/03/science/the-cute-factor.html">minor negative affects</a>: helplessness, pitifulness and excessive availability. These in turn summon a set of <a href="http://www.cabinetmagazine.org/issues/43/jasper_ngai.php">complex secondary reactions</a>: of resentment at being emotionally manipulated, contempt for the weakness of cute objects, and disgust at the cheapness of cute things. To judge something as cute can accompany a desire to touch, clasp, dominate and destroy it; in other words, it is something both pleasurable and disgusting. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/239098/original/file-20181003-52663-10e8plw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/239098/original/file-20181003-52663-10e8plw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/239098/original/file-20181003-52663-10e8plw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=484&fit=crop&dpr=1 600w, https://images.theconversation.com/files/239098/original/file-20181003-52663-10e8plw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=484&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/239098/original/file-20181003-52663-10e8plw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=484&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/239098/original/file-20181003-52663-10e8plw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=608&fit=crop&dpr=1 754w, https://images.theconversation.com/files/239098/original/file-20181003-52663-10e8plw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=608&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/239098/original/file-20181003-52663-10e8plw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=608&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The cute social world of bacteria, 1913.</span>
<span class="attribution"><a class="source" href="https://wellcomecollection.org/works/bjfmf43v?query=V0011623&wellcomeImagesUrl=/indexplus/image/V0011623.html">Wellcome Collection</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>It is small wonder, then, that the objects that are most often rendered as cute in consumer aesthetics – women, technology and children – are the ones that have been regarded as inherently dangerous and in need of control. And the uncomfortable truth is that this cuteness often places them as objects below ethical consideration, with the result that we feel no remorse in eliminating them.</p>
<h2>2. Overpopulated bacteria</h2>
<p>Second, bacteria don’t come in ones and twos. They flourish <a href="https://www.coroflot.com/williamtapp1979/Domestos-Millions-of-Germs-will-Die-Campaign-for-Lowe">in their billions</a>. This can be terrifying and it can awaken fears of overpopulation. Perhaps this is no coincidence – after all, the massive urban population growth of the 19th century was accompanied by a revulsion at the new bacteriological knowledge that we gained <a href="http://catalogue.wellcomelibrary.org/record=b1160239">thanks to the microscope</a>. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/239094/original/file-20181003-52674-1p5tf9x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/239094/original/file-20181003-52674-1p5tf9x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=408&fit=crop&dpr=1 600w, https://images.theconversation.com/files/239094/original/file-20181003-52674-1p5tf9x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=408&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/239094/original/file-20181003-52674-1p5tf9x.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=408&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/239094/original/file-20181003-52674-1p5tf9x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=513&fit=crop&dpr=1 754w, https://images.theconversation.com/files/239094/original/file-20181003-52674-1p5tf9x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=513&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/239094/original/file-20181003-52674-1p5tf9x.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=513&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Etching by W Heath, 1828.</span>
<span class="attribution"><a class="source" href="https://wellcomecollection.org/works/nfy5zycn?query=V0011218&wellcomeImagesUrl=/indexplus/image/V0011218.html">Wellcome Collection</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>This sketch of a woman horrified at the contents of her magnified tea dates from a period of exponential population growth in London, the dawn of Malthusian economics, a time when the Thames was an open sewer. The cramming full of many life forms into tiny spaces was an uncanny microcosm of the imagined, and feared, socioeconomic order. </p>
<p>This anxiety-laden pairing of overpopulation and bacterial proliferation continues to be provoked in visualising contemporary bacteria. Bacteria live in obscene proximity to each other, their intimacy an affront to the force of modernity, anathema to the grid of science and civic control. This historical confluence of factors means that bacteria became, and continue to be, a channel for fears about overpopulation, immigration and the corruptive influence of living too closely with millions of others. </p>
<h2>3. Poor bacteria</h2>
<p>Third (and this is a closely related factor) bacteria often seem to live in squalor and poverty. Their skin is slimy, their teeth and skin are unhealthy, and their clothes are <a href="http://www.advertisingarchives.co.uk/en/asset/show_zoom_window_popup.html?asset=40701&location=grid&asset_list=58036,49166,45403,45402,45400,43906,41557,40702,40701,39652,39651,39649,37616,23335,23321,22988,19685,19684,15895,15894,15893,15892,10920,10533,10061&basket_item_id=undefined">ill-fitting and dirty</a>. They are <a href="http://www.chinaadren.com/html/file/2010-5-6/20105600124.html">criminal</a>. </p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/QjaQdOXPJHU?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
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<p>This makes for a drastic contrast with the consumer, the person who uses antibacterial products. While “they” are lower-class, grimy and slothful, the <a href="https://www.coloribus.com/adsarchive/prints/dettol-instant-hand-sanitizer-dirty-stranger-15462705/">antibacterial person</a> is middle-class, reassuringly clean, and busy in her or his daily life.</p>
<h2>4. Sexual bacteria</h2>
<p>Fourth, bacteria seem to have no regard for “proper” sexual roles and behaviours. People who fail to use antibacterial products are associated with promiscuous, non-reproductive sexual behaviours.</p>
<p>One <a href="https://www.coloribus.com/adsarchive/prints/antiseptic-soap-alley-15954405/">2010 ad</a> visualised a woman in a red dress lying asleep in a dark alley on a pile of binbags, with the tagline “Don’t Go to Bed Dirty”. This is arguably a conflation of sexual promiscuity with bacterial promiscuity, at odds with the ideal of a bleach-white <a href="http://www.dettol.co.uk/new-mums-related-articles/pregnancy/tips-for-new-mothers-keeping-clean-and-pristine/">nuclear family</a>. </p>
<p>Another depicts bacteria treated with anti-bacterial as stereotypical homosexuals with the tagline “<a href="https://www.coloribus.com/adsarchive/prints/bombril-lysoform-gays-14372105/">germs just can’t reproduce</a>”. Yet another shows the <a href="http://www.adruby.com/print-ads/siribuncha-keep-your-moment-clean-instant-hand-sanitizer">archetypal besuited middle-class man</a> surrounded by the traces of bacterial others who have been at the toilet cubicle before him, including a transvestite. And let’s not forget of course the <a href="https://profiles.nlm.nih.gov/ps/retrieve/ResourceMetadata/VCBBCB">long history</a> of war propaganda warning soldiers on leave to avoid sexual contact with women, who were equated with bacterial disease.</p>
<h2>Why it matters</h2>
<p>This sketch of the ways that bacteria appear in popular culture is also a sketch of ourselves. What our research demonstrates is that bacteria are a kind of vehicle for fears of what we might be, and of aspects of ourselves and our society that we find it difficult to confront directly.</p>
<p>Unfortunately, this has disastrous consequences for our planet and for the things that live on it, which of course includes us and bacteria. We’re stuck together: there are about five million trillion trillion of them on this planet; if every one of them were a penny, the stack would stretch a <a href="https://www.sciencedaily.com/releases/1998/08/980825080732.htm">trillion light years</a>. They are a complex, ancient entity.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/239102/original/file-20181003-52666-1ajuob8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/239102/original/file-20181003-52666-1ajuob8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=390&fit=crop&dpr=1 600w, https://images.theconversation.com/files/239102/original/file-20181003-52666-1ajuob8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=390&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/239102/original/file-20181003-52666-1ajuob8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=390&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/239102/original/file-20181003-52666-1ajuob8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=491&fit=crop&dpr=1 754w, https://images.theconversation.com/files/239102/original/file-20181003-52666-1ajuob8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=491&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/239102/original/file-20181003-52666-1ajuob8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=491&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Leptothrix bacteria.</span>
<span class="attribution"><a class="source" href="https://wellcomecollection.org/works/ejhtfwjv?query=bacteria">Wellcome Collection</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
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<p>But the visual vocabulary of fear, disgust and dread that has been so effective at selling antibacterial products for well over a century has brought us to an ecological dead end. Our overuse of antibiotics is the most obvious evidence of the failure of the demonise-and-destroy approach that antibacterial thinking produces, leading to a market failure that some experts posit is <a href="http://www.who.int/drugresistance/documents/surveillancereport/en/">bigger than climate change</a>. </p>
<p>A totally new understanding of bacteria as a realm that we must live within, from which it is foolhardy to think we can escape, is needed. An important step in that direction is describing the destructive ways of thinking about bacteria that have stepped in between us and these necessary cohabitants of our planet.</p><img src="https://counter.theconversation.com/content/103944/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Our view of this essential dimension of earth’s biome has been shaped by the manufacturers of cleaning products.Norah Campbell, Assistant Professor in Marketing, Trinity College DublinCormac Deane, Lecturer in Media, Dún Laoghaire Institute of Art, Design and TechnologyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/921022018-02-21T05:03:39Z2018-02-21T05:03:39ZWhy we developed a microscope for your phone – and published the design<figure><img src="https://images.theconversation.com/files/207206/original/file-20180221-161929-1iqfjtt.png?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Soon you could be looking at microscopic creatures with your mobile phone. </span> <span class="attribution"><a class="source" href="https://www.nature.com/articles/s41598-018-21543-2">Scientific Reports</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>My colleagues and I have developed a 3D printable “clip-on” that can turn your smartphone into a <a href="https://www.nature.com/articles/s41598-018-21543-2">fully functional microscope</a>. </p>
<p>We’ve released the design <a href="http://cnbp.org.au/online-tools">online</a> so that anyone can print it and modify it to suit their needs. </p>
<p>But why? </p>
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Read more:
<a href="https://theconversation.com/blood-tests-and-diagnosing-illness-what-can-blood-tell-us-about-whats-happening-in-our-body-80327">Blood tests and diagnosing illness: what can blood tell us about what's happening in our body?</a>
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<p>For a lot of medical diagnostics, you need to look at small stuff – down to the level of individual cells. To do that, you need a microscope. </p>
<p>There’s been a push over the past decade or so by scientists and engineers to bring diagnostics into the home, and to other areas where you can’t really bring traditional lab equipment.</p>
<p>Scientists are hoping that this will allow them to, for example, <a href="https://www.nature.com/articles/srep13368">detect malaria</a> and other <a href="http://stm.sciencemag.org/content/7/286/286re4">blood borne parasites</a> in the field in Africa. </p>
<p>And the backbone of a lot of portable medical diagnostic devices is a mobile phone-based microscope. </p>
<h2>A good place to start</h2>
<p>You may not think of your mobile phone as being anything like a microscope, but it has almost all the parts you need. The lens and camera sensor are arranged exactly as they would be inside a microscope – all you need to do to get some magnification is stick another lens in front. </p>
<p>The next part is to think about how you are going to illuminate your sample, which is often just as important as the lenses you use. </p>
<p>There’s been a lot of great work over the past decade or so engineering mobile phone microscopes with amazing capabilities – for example, <a href="http://cellscope.berkeley.edu/">the Fletcher lab at UC Berkeley</a>, and <a href="http://innovate.ee.ucla.edu/">the Ozcan lab at UCLA</a> – and a lot of it has to do with custom illumination. </p>
<p>The engineering involved to assemble these mobile phone microscopes is not trivial, however. You often need a decent amount of skill and a lab to be able to put these devices together. We wanted to see how simple we could make a microscope, meaning the fewest extra parts and assembly steps possible. </p>
<h2>Guiding the flash</h2>
<p>We figured that it made a lot of sense to use the internal flash in the camera to light up your sample. The challenge is that the flash points in the wrong direction – you need to turn it around to shine through the sample and into the camera.</p>
<p>Redirecting light like this usually requires something fancy like a mirror or a prism. But we realised that the flash on a phone is so bright we can just use the diffuse reflection (glare) off regular plastic. So we designed the clip to have a series of tunnels that confine light and turn it around to face the sample and camera. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/207201/original/file-20180221-161923-150t9id.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/207201/original/file-20180221-161923-150t9id.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=340&fit=crop&dpr=1 600w, https://images.theconversation.com/files/207201/original/file-20180221-161923-150t9id.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=340&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/207201/original/file-20180221-161923-150t9id.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=340&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/207201/original/file-20180221-161923-150t9id.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=427&fit=crop&dpr=1 754w, https://images.theconversation.com/files/207201/original/file-20180221-161923-150t9id.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=427&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/207201/original/file-20180221-161923-150t9id.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=427&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Left: Wireframe schematic of the clip on device. Flash illumination is indicated by the blue arrow. Upon striking the illumination backstop (made of the same 3D printed resin as the rest of the clip), this light is reflected diffusely towards the sample and then through the lens into the camera. Right: Cutaway 3D model of the clip-on device, showing the illumination tunnels.</span>
<span class="attribution"><a class="source" href="https://www.nature.com/articles/s41598-018-21543-2">Scientific Reports</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>A lot of light is absorbed by the 3D printed resin of the clip, which is black. But it’s not perfectly black, and even the tiny fraction of light that makes it through the tunnels and reflects off of the black surface is more than enough to light up a microscopic sample. And that’s it – no mirrors, prisms or illumination lenses are needed. </p>
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Read more:
<a href="https://theconversation.com/explainer-how-scientists-invent-new-colours-80897">Explainer: how scientists invent new colours</a>
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<h2>Light and dark</h2>
<p>Next, of course, you need something to look at. The local pond is a good place to start. Put some water on a slide or in a capillary tube and you will find many cool-looking microorganisms going about their lives. </p>
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<figcaption><span class="caption">A microorganism viewed with the mobile phone microscope.</span></figcaption>
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<p>This type of illumination is called bright-field microscopy. But we actually went a bit further, and showed that you can turn the flash off and use the Sun to perform dark-field microscopy - where the specimen is lit up, but the field around it is dark.</p>
<p>The clip is designed in such a way that sunlight (or ambient room light) gets trapped in the glass sample slide, and can only be redirected into the mobile phone camera if it hits an object in the sample. If the sample slide is empty, the background is dark (hence dark-field). If there is an object it shines bright on the dark background, and as such this is a great way to detect really subtle objects such as cells (which are mostly water) sitting in water.</p>
<p>What we’re hoping is that our design, or something like it, gets used for ultra simple, cheap and robust mobile phone based devices – be it for medical diagnostics in underserved areas such as the remote Australian outback and central Africa, or monitoring microorganism populations in local water sources. </p>
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<strong>
Read more:
<a href="https://theconversation.com/how-weve-evolved-to-fight-the-bugs-that-infect-us-75057">How we've evolved to fight the bugs that infect us</a>
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<p>We’ve released the design <a href="http://cnbp.org.au/online-tools">online</a> so that anyone can print it and modify it to suit their needs. This part is important because the mission of low-cost microscopy is to ease access to this high tech equipment. This is best accomplished when everyone has the opportunity to make one for themselves or to adapt it freely.</p>
<p>The clip can be printed using any 3D printer - we prefer the <a href="https://formlabs.com/">Formlabs</a> family of printers - and you’ll need black resin. The cost in resin per clip is typically a couple of dollars at most. You’ll also need a lens to put in the clip. We buy ours from an <a href="http://www.wholesaleiphoneparts.com.au/">online retailer</a> and then remove the lens from the camera module.</p><img src="https://counter.theconversation.com/content/92102/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Antony Orth receives funding from the Australian Research Council. </span></em></p>Even though you don’t think of your mobile phone as being anything like a microscope, it’s got almost all the parts you need.Antony Orth, Research Officer , RMIT UniversityLicensed as Creative Commons – attribution, no derivatives.