The creator of genetically-engineered “marathon mice,” Dr. Ronald Evans conducts pioneering research into the molecular mechanism of how our cells to burn fat. A professor at California’s Salk Institute of Biological Studies, and recipient of a 2006 Gairdner award, he discussed the scientific and ethical implications of metabolic engineering at the Gairdner Foundation public lecture on October 24.
Central to Evans’ research are a class of molecules called the nuclear hormone receptors that surround the cell’s nucleus.
“All organisms must get energy to survive from their environment, which they cannot manufacture on their own,” said Evans. “Every genome has built into its molecular code a way to get the energy it needs from the environment.”
The energy cells need can be obtained by burning fat. The nuclear hormone receptors responsible for fat burn are the PPARs, peroxisome proliferator-activated receptors, a family of nuclear receptors in nearly every cell type. While all PPARs bind to fat, the three forms (alpha, gamma, and delta) work in concert to regulate the amount of fat in our body. Alpha and delta are responsible for burning fat, and gamma for storing fat.
By genetically engineering mice to express larger-than-normal amounts of PPAR delta, Evans created mice that were able to burn more fat over time, improving their access to a long-term storage of energy. Evans tested for superior physical endurance in a “marathon mouse” treadmill experiment where normal mice and genetically-engineered mice were placed on treadmills and ran until fatigued. The marathon mouse ran twice as long as the non-genetically engineered mouse.
In today’s society, high levels of obesity and diabetes make Evans’ research extremely important. In the U.S., about one in five children become diabetic each year, which increases their chances of developing heart disease and hypertension.
“Obesity has to do with problems of metabolic control, where the molecular switches that control rate of fat burning in our cells go awry,” said Evans. These studies open up possibilities for developing a drug which would activate the PPAR molecules and melt fat away.
Indeed, Evans and his team developed a drug which improves the endurance of marathon mice by 80 per cent. However, this drug is only effective when the mice had previous physical training.
“So the drug is ineffective without the maintenance of exercise-no pain, no gain,” said Evans.
While Evans’ drug discovery has many positive implications for use in the treatment of obesity, muscular dystrophy and diabetes, many people are concerned about athletes abusing his discovery to enhance their performance.
“Most scientists are principally devoted to their science at such a level that they are not involved in the social implications of their work,” said Evans.
