Scientists Paralyze and Then Cure Worms

Photo: Scientists paralyze and then cure worms: Canadian researchers use light to turn potential drugs on, and then offAmerican Chemical Society
This tiny worm became temporarily paralyzed when scientists fed it a light-sensitive material, or "photoswitch," and then exposed it to ultraviolet light.

Ever since a Canadian team of scientists revealed they had figured out how to paralyze worms - and then cure the paralysis - just by flashing the worms with different beams of light, Neil Branda has been asked the same question over and over.

What animal is he going to paralyze next?

None, as a matter of fact, he says.

The worms simply served as a dramatic confirmation of the first known ability to use light as a means of switching a biological function on and off, and it could have major implications for fields ranging from optical memory to medical surgery in humans.

Light switching has been used for years in non-biological systems, such as transition lenses that darken when exposed to light, and then reverse the process when the light dims. But this is different.

"Nobody we know of has put light switching into live organisms and then shown a reversible biological effect, at least to the best of our knowledge," chemist Neil Branda, leader of the team of researchers at Simon Fraser University in British Columbia said in a telephone interview. The findings were published in the current issue of the Journal of the American Chemical Society.

Visible Light Activates and Reverses Paralysis

The researchers designed a molecule that "for several complicated reasons" they thought would induce paralysis in tiny transparent worms, C. elegans, when exposed to ultraviolet light.

The molecule was dissolved in an aqueous solution and then "orally administered" to hundreds of nematodes, which turned blue and went into paralysis. That was expected, because similar experiments have been done in labs around the world.

However, when the worms were hit with visible light, the process was reversed and the nematodes regained their mobility and appeared "as if they had never been paralyzed," the study reports.

Why is that such a big deal? Light is already used to switch on biological functions for treatment of arthritis and several types of cancer, called photodynamic therapy, but once the process is switched on, it can't be switched off.

Thus the drug remains active for some time - at least four weeks according to the Mayo Clinic - so patients have to avoid bright lights for six weeks to keep the activated drug from doing extensive damage elsewhere in the body.

Could Light-Switching Technology Someday Treat Cancer?

But if the process can be reversed - turned off by light - then the drug can be deactivated immediately after it has finished its task.

"That's the main concept we were trying to prove, the ability to get both spatial and temporal control exactly when and where the drug can be activated in a living organism," Branda said.

"One of the problems with photodynamic therapy is that all drugs are toxic, of course, but you want them to be toxic only to the cells you want to kill," Branda said. But once the drug is turned on "it keeps doing whatever you designed it to do. If it swims away from the site and starts doing things in the body that you don't want it to do, we have the potential to turn it off."

If this technology lives up to its promise, it may someday be possible to flood the body with designer molecules that with a flash of light could activate a drug in a precise area to treat something like cancer, destroy the cancer cells at that site, and then be switched off and thus avoid damaging healthy cells, now one of the major drawbacks of various cancer treatments.

Technology Could Help Scientists Reach 'Holy Grail' of Neurological Surgery

This is a long shot, but the technology may eventually help scientists tackle the "holy grail" of neurological surgery.

The human brain is protected by the blood-brain barrier, which blocks entry to the brain of nearly anything that is not normally part of the process. Thus drugs, which could treat an inoperable brain tumor, can't get past the barrier.

But if the drugs could masquerade as a chemical that is friendly to the brain, and then activated once it is inside, and deactivated after it finishes its assignment, many lives could be saved.

And you can make a molecule look like something it isn't just by changing its shape.

"In biology, shape is one of the key factors that dictate the function of a molecule," Branda said. "The chemical that makes caraway seeds smell like caraway seeds is identical to the molecule that makes spearmint smell like spearmint, except they are mirror images of each other. The nose has receptors that are so sensitive they can sense not just the shape of a molecule, but the three-dimensional handedness of the molecule, whether it's left handed or right handed."

Light-Switching Still in Realm of Basic Research

So you design a molecule that looks left handed - and thus relatively harmless - and get it to wherever in the body you want it to go, and then hit it with light and change it to right handed so it can kill cancerous cells. Then you turn it off.

Of course, there are still some tough challenges ahead. The Canadian researchers used ultraviolet light to turn their molecules on, but that light is extremely toxic, as anyone who has spent too much time in the sun knows. UV light is probably out.

"So you have to be able to harness light and use light in creative ways that's less damaging," Branda said.

In earlier research, Branda's team added a nano-particle to their molecule, which absorbs infrared light, which is far less harmful to human tissue. The nano-particle acts as an antenna, absorbing the red light, which is then converted internally to ultraviolet or visible light, depending on whether the molecule is to be turned on or off. So the UV light is restricted to the precise area where the molecule is to do its work.

All of this, of course, is still in the realm of basic research. Many labs are working on the same problem, trying to develop ways to use light to control biological functions in a very precise way, turning them on when they are needed, and off when they aren't.

By the way, whatever happened to all those worms? Many survived through multiple replications of the experiment, but in the long run, it proved too toxic. They all eventually died.