Scientists Excited About Miniature Cooking Pots

07/02/98 BOZEMAN -- Most people have a favorite cooking pot, like a saute skillet with a wooden handle or a copper-bottomed sauce pan.

Right now Mark Young is pretty excited about what may be nature's smallest cooking vessel--the round shell of a virus that's been emptied of the stuff that causes disease.

Young studies viruses at Montana State University-Bozeman. He and Temple University chemist Trevor Douglas have discovered that the protein case that encapsulates a virus can be hijacked when empty and used as a "molecular cooking pot" of the nanosphere size. That's one thousand millionth of a meter.

In this scenario, viruses would work for us. Such a minuscule vessel could travel inside the body and deliver a drug to the right cellular address, for example.

"What you have is a container," said Scripps Research Institute virologist Jack Johnson. "It allows you to do chemistry on an exceptionally small scale."

He said the applications could be widespread because the goal of much of modern technology--from biology to electronics-- is to make things as small and as uniform as possible.

Last month, Young and Douglas published a paper on the discovery in the international journal Nature. Since then, the response from the scientific community has been "incredible," said Douglas.

Chemists have been trying to build cage-like structures for years, thinking they would be useful for making materials of unique value or materials that would have unique properties, Douglas said. But the results were mixed. The size wasn't always uniform, and hence, neither were the properties.

Instead of building the cages one molecule at a time, Young and Douglas are stealing them.

"The natural role for that shell is to transport [the virus]," said Young. "It evolved to survive in many different chemical environments. We're just hijacking nature."

Some shells are rod-shaped, some are spheres. Many are well enough studied that scientists know their exact size and shape inside and out.

The shells, or pots, have lids that can open and close, so Young envisions chemicals going into the pot, a chemical reaction occurs, the lid closes, the pot gets transported to another location, the lid opens and out come the contents.

Young said the approach is so new that when the patent application was filed, a patent search yielded nothing even remotely similar.

"The idea was everything," said Young. "It was so obvious once the connection was made that we had to keep quiet about it."

Their collaboration began after Douglas, who until a year ago taught chemistry at MSU-Billings, was looking through a news magazine and saw a picture of HIV. It looked a lot like a protein he studies called ferritin.

"I thought, 'Gee. Maybe they have a similar function'," he recalled. "Both are storage containers. Ferritin stores iron. A virus stores nucleic acids."

Later, he met Young, an internationally known plant virologist.

"I said, 'This is pretty out to lunch, but I need an empty virus'," Douglas recalled.

"The real thinking was, 'Let's not think of the shell as part of the infectious agent,' Young said. 'Let's think of it as a molecular-sized cooking pot, a constrained reaction vessel where the size and shape of the vessel are determined by the virus'."

One application is targeted drug delivery where the pots take the medicine to the correct spot in the body. The team is trying to develop such a system for breast cancer treatment. They just received a $375,000 grant from the National Science Foundation to apply the discovery to medical diagnostics.

"Before this work, no one knew how to make a homogeneous environment for getting all the same size and shape of material," said Young. "This is a huge shift in thinking."