Working on thin ice
By Lindsay Forcellini

Robert Ben, a professor at the University of Ottawa, is currently working on developing an analog that will inhibit the growth of ice.

OTTAWA — In his synthetic organic chemistry lab at the University of Ottawa, researcher Robert Ben is working on thin ice. And it’s getting thinner.

Ben and his team of researchers are studying antifreeze glycoproteins, a novel class of compounds that possess the ability to inhibit the growth of ice.

These compounds can be found in various fish, plants, amphibians, and insects. Ben’s research focuses on the antifreeze derived from fish.The long-term goal of this research is to find new and effective ways to preserve cells, tissues, and ultimately, organs.

When an organ is frozen, explained Ben, ice crystals develop within the tissues, leaving holes in the cells once the organ is thawed. It is these holes that are problematic and very damaging to the organ.

"Our research is important largely because . . . there is only a 10 to 16 hour window for donor organs, so lots of them aren’t donated at all," Ben said. "If we could freeze organs, we could alleviate the shortage, and ultimately, less people would die."

Ben’s research is based on analogs of a compound that is naturally occurring in fish.

An analog has a molecular structure very similar to the native compound but with distinct differences. Often the analog is a simplified version, noted Ben, and it is created using medicinal chemistry to enhance the stability of the compound.

"Say you have a car and you don’t know how it runs. You can take the door off and it will still run, so you deduce that the door isn’t important. But if you go under the hood and remove the spark plugs, the engine won’t start," Ben said."Medicinal chemistry involves making small changes to the analog to monitor its functional activity to deduce what is important."

Once the analog is structured, the researchers make it in the lab and then test it. Ben said testing is performed using mammalian cell lines, or cell cultures because if the compound does not work on the culture, it will not work on the organ. The testing process takes about one week per analog.

"We’ve probably made about 60 analogs to date, and it’s still a learning curve. It really is an ongoing process," noted Ben.

The researchers are at a crucial point in the project, having discovered that the compound has other interesting biological properties.

"We discovered, by accident really, that it has applications in the treatment of stroke and spinal cord injuries,"explained Ben. "So in the next year, we will be exploring these unique properties."

The team will also be patenting its research in the coming months, but Ben said his interest is more in the complexity of the science and finding out how the compound actually works rather than patenting the theory just to make money.

Ben’s research is also unique in itself. While there are a handful of labs around the world that are working with antifreeze compounds, Ben proudly stated that his lab is the only one in the world to create a new analog based on a natural structure.

"We’ve gone one step further," he says. "It buys us a little niche."

Having obtained an undergraduate degree in bio and organic chemistry at Laurentian University, Ben, who was born in Sault St. Marie, Ontario, later completed his Ph. D. studies in synthetic organic chemistry at the University of Ottawa. His post-doctoral work was done at the University of Toronto where he was later hired by the National Research Council. Ben later worked in the United States for five years before moving his lab back to Canada and the University of Ottawa.

In the mid-1908s, Ben said he was reading literature about a compound that allowed organisms to survive sub-zero temperatures, so he looked up the structure.

"I thought it would be a great program to initiate. It started off really quickly," he explained.

Ben said his education and training has really paved the way. His research has already earned him awards, including the Ottawa Life Sciences Council award for most promising scientist this past September.

"We’ve received a great deal of recognition and media coverage. We’ve been lucky,” said Ben. "Our research has been met with warm reception in general. Everybody can relate to ice and can understand the problems it can cause."