EDFORD, Mass. — They look like little more than grayish-black grains of couscous floating in water.
But they are actually African clawed frogs-to-be, replete with minuscule blobs that will become eyes. “These little beans here are what I do the surgery on,” said Douglas Blackiston, a postdoctoral fellow at Tufts University’s Allen Discovery Center, holding out a Petri dish.
On Thursday, Blackiston published the results of a few years’ worth of those microscopic surgeries, and the finding is bizarre: If you transplant an eye onto what will become the tadpole’s tail, that organ — misplaced though it may be — can allow the animal to see.
Admittedly, it’s impossible for humans to look through a clawed frog’s eyes, and in this case, Blackiston and the director of his lab, Michael Levin, were mainly testing whether the tadpoles could perceive movement and colored light. But they say their research doesn’t just have implications for scientists’ ability to restore vision; it also sheds light on how to connect implants and grafts to the body’s own wiring.
“You implant these organs, but you want them to be functionally integrated with the host nervous system otherwise they aren’t going to work,” said Levin, the lead author of a paper published Thursday in Nature Regenerative Medicine. Do you have to “connect up every neuron,” he wondered, or can you make use of the natural ability of the nervous system to adapt and rewire itself?
To understand just how malleable our sensory systems are — and to try to find a way for the blind to see again — scientists have already rerouted visual information into the channel normally used for touch. Levin calls the resulting technology “the electric lollipop”: It involves a camera that converts images into little electrical charges. There are few areas of the body sensitive enough to feel subtle differences in those little bursts of electricity besides the fingertips and the tongue, so patients hold a device in their mouth. And with training, they are able to feel the shape and position of whatever is in front of them to such an extent that the brain areas normally associated with vision are activated.
“If I throw the ball across the desk, and you are watching through the camera and the tongue, you can catch it, and you can learn it in a matter of a couple of hours,” said Yuri Danilov, a neuroscientist who has worked extensively on that device at the University of Wisconsin-Madison’s Tactile Communication and Neurorehabilitation Laboratory.
But Blackiston and Levin wanted to see whether they could get a transplanted eye to produce a network of nerves that would connect up to the central nervous system. A few years ago, they found that they could encourage nerve-growth by fiddling with the electrical charges in cells. But could they do something similar using just a drug?
To find out, Blackiston began by taking out the eyes of some of those early stage tadpoles with tweezers. Then, he made tiny slits in what would soon be the tail — “These are embryos, so they are Play-Doh consistency,” he explained — and into each slit he dropped another tadpole’s eye.
“It all just heals together, the wound is invisible within 10 to 15 minutes,” said Blackiston. “You can’t even see where you’ve done the surgery.”
Then he let them grow. Some of the tadpoles got a dose of a human migraine medicine called zolmitriptan, which the researchers thought might promote nerve growth; other tadpoles just got the plain old salty water that they are usually kept in.
Tadpoles, though, aren’t much good at answering questionnaires about what they are able to see. Instead, the researchers created what amounts to a psychology lab for amphibians. It looks a little like a black box in which a magician might cut an assistant in half. At the top is a series of chambers where the tadpoles can swim. When the scientists close the lid, lights are flashed down onto the animals from above, and their movements tracked by cameras below.
By programming electric shocks that kick in when red is flashed, the researchers can train tadpoles to associate that color with pain. Yet only those that are able to see color will be trained, and will swim from the red light into the blue.
Like normal, seeing tadpoles, the ones that got the graft and the medication were able to detect the red, and would wriggle their way into another patch of color. They were also able to follow moving triangles, reversing direction when the shapes did, much as they would if they were swimming along with a group.
Grafted animals that did not get the medication, though, didn’t do so well.
The tadpoles from which the eyes were taken had been modified so that any nerves growing from the transplanted organs would glow bright red in certain conditions. When Blackiston put the medicated tadpoles in fluorescent light under a microscope, he saw their tails lighting up with tendrils of red: They were new nerves carrying information into the central nervous system. When he did the same for the non-medicated tadpoles, he could see the neurons in the grafted eye glowing red, but very few of them sent out any new nerves.
“What’s new here is that … an eye that is not properly connected to the central nervous system nevertheless provides a sensory input that the animal can use to orient itself,” said Bernd Fritzsch, a biologist at the University of Iowa who has done similar experiments.
Danilov, the Wisconsin neuroscientist, is not convinced that this finding could be translated into humans any time soon.
Blackiston and Levin know that this isn’t ready to be tried in humans. But what’s exciting to them is that a drug already used by people with migraines seems to help nerves grow from implants, without disrupting any of the other nerves in the body. For now, it only works in tadpoles, but it’s a start.