In general, our knowledge of biology—and much of science in general—is limited by our ability to actually see things. Researchers who study developmental problems and disease, in particular, are often limited by their inability to look inside an organism to figure out exactly what went wrong and when. Now, thanks to techniques developed at Caltech, scientists can see through tissues, organs, and even an entire body. The techniques offer new insight into the cell-by-cell makeup of organisms—and the promise of novel diagnostic medical applications. "Large volumes of tissue are not optically transparent—you can't see through them," says Viviana Gradinaru (BS, 2005), an assistant professor of biology at Caltech and the principal investigator whose team has developed the new techniques, which are explained in a paper appearing online on July 31, 2014 in the journal Cell. Lipids throughout cells provide structural support, but they also prevent light from passing through the cells. "So, if we need to see individual cells within a large volume of tissue"—within a mouse kidney, for example, or a human tumor biopsy—"we have to slice the tissue very thin, separately image each slice with a microscope, and put all of the images back together with a computer. It's a very time-consuming process and it is error-prone, especially if you look to map long axons or sparse cell populations such as stem cells or tumor cells," she says. The researchers came up with a way to circumvent this long process by making an organism's entire body clear, so that it can be peered through—in 3-D—using standard optical methods such as confocal microscopy. The new approach builds off a technique known as CLARITY that was previously developed by Gradinaru and her collaborators to create a transparent whole-brain specimen.
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