Transparent mice

See through mouse 1

California Institute of Technology scientists developed a chemical technique to make dead mice transparent to help researchers see how disease spreads through the body, map the nervous system, and other projects.

"Our methodology has the potential to accelerate any scientific endeavor that would benefit from whole-organism mapping, including the study of how peripheral nerves and organs can profoundly affect cognition and mental processing, and vice versa," says Caltech researcher Vivian Gradinaru.

"Our easy-to-use tissue clearing protocols, which employ readily available and cost-effective reagents and equipment, will make the subcellular interrogation of large tissue samples an accessible undertaking within the broader research and clinical communities."

(The Independent)

Notable Replies

  1. I just vomited in my mind a little.

  2. Cool! Too bad it does not work (yet?) on live ones; all sort of fluorescent markers would then be possible to watch in real time.

    ...thought... could the fluorescent markers be used anyway, along the lines of infrared tomography? Tissues are quite translucent for near-IR, and a suitable fluorophore could be excited with near-IR, emit in slightly less near IR (both wavelengths in the tissue low-absorbance window), and have short-enough response to react instantly-enough to the excitation pulse to make time-of-arrival detectors useful...

  3. "I am a great soft jelly thing. Smoothly rounded, with no mouth, with pulsing white holes filled by fog where my eyes used to be. Rubbery appendages that were once my arms; bulks rounding down into legless humps of soft slippery matter."

    As much as that's totally awesome, and definitely going to prove scientifically useful, I must admit that the above was my first thought on seeing the image...

  4. Funny that they didn't show an image of the researchers

  5. Neuroscience grad student here: Yes, there are a few methods to render dead tissues (mostly brains, for what I know) transparent, most developed in the past few years, and to varying degrees with a mad-sciency touch to them. The most famous is called CLARITY: It essentially covers all cell membranes in the brain with plastic, then washes said cell membranes away, leaving an almost-transparent aerogel with all the structures (nominally) intact. Others, such as ClearT, replace the watery solution in the cells with foramic acid, which also renders the cells transparent. All those techniques are essentially workarounds for the fact that the water-lipid-water junctions of cell membranes vs. the outside world scatter light. Thus, either the lipids or the water need to be replaced to make the brain transparent. Brains are easy in that regard, because they are just big lumps of fat and proteins without any bones or rigid structures.

    On living tissue, it's a different story: Yes, there are techniques which allow you to record fluorescent markers in a living brain, but those all include opening the skull and getting a microscope inside. With a high-powered microscope (such as a 2-photon microscope), you can even see the changes in different synapses over seconds, near the resolution limit of optical microscopy. This only works for the first few hundred micrometers though (remember, the brain is a lump of mostly fat and therefore pretty intransparent), roughly equivalent to the top third of the outermost layer of the mouse brain. Through the skull would not work, beacuse even for mice, it's too thick and scatters the light too much. Making them transparent would help, but up to date, that includes pretty nasty chemicals and week-long incubations, not to mention high-voltage shocks needed for some protocols. [Edit: None of which work while the skull's owner is alive.]

    There is a technique called functional near-infrared spectroscopy, that shines near-infrared light on the skull, in the hope that some portion of it gets reflected by the blood pulsating through the brain. That seems to be promising at least, but there you measure in the range of centimeters due to the scattering by the skull. So, even if you got the appropriate red-shifted flourescent proteins (which are the hardest to make due to the low energy density of IR light) in there, the skull's bone would probably scatter too much to see anything clear enough.

    But what if you could make the light do something with only a one-way trip? There is a report about red-shifted channelrhodopsins, relatively simple proteins that make neurons light-sensitive (and are on the fast track to revolutionize neuroscience). In this case, the channelrhodopsin is sensitive to dark red, which already penetrates bones and tissues reasonably well. With those, you could (in theory) activate neurons through the intact skull, giving completely new, well controllable input from the outside. Appropriately, the authors named their creation ReaChR (paywalled article here, useable summary here). Maybe that's what you're looking for for your mad-scientist ambitions? wink

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