Seeking the molecular Fountain of Youth
By Christine Boyd

The spokes and globes that shimmer and wheel slowly on Jim Wright's computer monitor resemble Tinker Toys — but to him, they could be the Fountain of Youth.

Wright, a chemistry professor at Carleton University in Ottawa, is trying to design a molecule he hopes might someday be able to help slow down heart disease, cancer, arthritis and aging.

In November 2000, Wright and the five other members of the team received a three-year $413,360 grant from the Natural Sciences and Engineering Research Council (NSERC) to try to create what Wright describes as a "souped-up version" of Vitamin E and study its effects.

The goal is to create a molecule that can combat free radicals — unstable oxygen molecules that wreak havoc.

"Free radicals are like wolves and our bodies are made out of molecules which are like a herd of moose," Wright says. 

"In that herd, there are some weak links — the very old, the crippled, the very young. That's us. That's our DNA, our proteins, our fats. The wolves pick off these weaker members." 

Electron knights storm the castle 

Every cell in the human body is powered by oxygen. Just as a car produces carbon dioxide when it burns gas, these cells give off "emissions" when they burn oxygen. The byproduct is oxidants, or free radicals — molecules that lack an electron. Normal human metabolism isn't the only way free radicals are created: they also spring from cigarette smoke, radiation, sunlight, air pollution and bad diet. 

But no matter how they're created, all are highly volatile molecules that try to steal electrons wherever they can.
Healthy cells can normally fight off these electron bandits. But when cells are damaged or become less efficient as the body ages, free radicals can wreak havoc.

Picture knights storming a castle. In their insatiable quest for oxygen, the free radicals will attack virtually any part of the cell. They pillage electrons from molecules in the cell walls, for example, setting off chain reactions that either make the walls too stiff to do their jobs or so weak that the innards leak out. 

But the most ominous destruction occurs within the mitochondria, the cell's power plants, which break down fats, carbohydrates and proteins to produce energy. In the process, free radicals are created. 

The mitochondria house a single DNA ring molecule. When free radicals attack the ring, they can trigger mutations.

Just as exposure to oxygen browns apples, rusts metals and turns butter rancid, this "oxidative stress" eats away at the body over time, eroding its ability to use energy efficiently. 

And that leads to disease. Free radical damage has been linked to cancer, heart disease, diabetes, arthritis, cataracts, fatigue, hardening of the arteries and a number of neurological diseases, including Lou Gehrig's, Parkinson's and Alzheimer's.

Attack of the antioxidants 

But there is a tool to fight free radicals — antioxidants. Antioxidants work by slowing down the chemical reactions that turn the normally stable oxygen molecule into a free radical. 

Antioxidants such as beta carotene and Vitamins C and E can be found in several food products, including apples, wine, green tea, carrots and tomatoes. But targeting free radicals with antioxidants is easier said then done. There are about 100 antioxidants and the way they work isn't always clearly understood.

The "Super Vitamin E" molecule spinning on Wright's computer monitor has been designed with an electron that has a weak bond, tempting free radicals to steal it — but not so weak that even the oxygen in air could set it off.

In other words, he hopes the molecule will be able to "step between the wolves and moose," in essence "sacrificing" itself for the greater good.

"The role of the antioxidant is to be a sacrificial weak member who dies rather than the rest of the herd. It would react with the free radicals faster than the free radicals can react with the DNA, proteins and fats." 

So far, the research has gone very smoothly, Wright says. Although the original grant only aimed at six molecules, he had already designed 50 models by November. Eight are already being tested on leukemia cells and the team hopes to finish on schedule within two years.