We can now make shrunken, see-through rodents for science

In a lab in Germany, researchers are making shrunken, see-through rodents. Don’t worry, it’s not as macabre as it sounds. Rather, this new method is a step forward for science because it’s the first time we can image whole animals at once and see how their organs work together. In fact, the researchers hope it’ll actually cut down on the number of rats we need for animal testing.

In a study published today in Nature Methods, researchers led by Ali Ertürk at Ludwig Maximilians University of Munich developed a technique that shrinks rodents by up to 65 percent, makes them transparent, and preserves key fluorescent proteins needed for imaging. Wonderfully, they call this technique “ultimate DISCO,” or uDISCO, which sounds like a disco dance school in Palo Alto.

It’s not easy to look at the cell structures of tissue. Currently, researchers can slice tissue into sections and image each slice individually, but then a lot of info about how cells and systems work together gets lost. A comparably new method called 3DISCO, or 3D imaging of solvent-cleared organs, also developed by Ertürk, shrinks the animals so we can fit more of them at once under the microscope, and also makes them transparent.

But 3DISCO quenches fluorescent proteins before scientists have time to prepare an entire body for imaging. Preparing an entire rat body can take up to a week, and imaging large samples can take several days. When the fluorescence signal fades in a couple of days, like with 3DISCO, there’s not much left to see in the tissues, says Ertürk.

With uDISCO, scientists added a solvent that not only makes the mouse more transparent than ever before, but preserves fluorescence for months. This gives them enough time to prep and image the entire (shrunken, transparent) body without losing the signal. The technique doesn’t significantly change the structures of the brain, and researchers can use it to study the circulatory system and nerve connections of rodents.

To better explain the process, Ertürk uses the metaphor of plumbing. If you want to see how pipes are organized in a building, the easiest way would be to make a wall transparent. The new technique also shrinks the building so all of it — and not just a wall — can become transparent. Next, let’s assume the pipes are transparent as well. To make it easier to tell the pipes from the glass wall, you could fill them with colorful water so they stand out more. This is how fluorescent imaging works, and why it’s so important to make sure the fluorescence doesn’t go away before you have a chance to carefully look at everything.

This method could be used on small monkeys and even an entire human brain in the near future, says Ertürk. And, now that we can see everything inside an animal at once, we can use fewer of them for imaging in the first place. And maybe one day, BodyWorlds?