Jan. 17) -- Manuel Uribe hasn't left his bed or his apartment in Monterrey, Mexico, in five years. That's because less than a year ago, at 1,200 pounds, he was considered by many to be the heaviest man in the world.Currently on a diet -- he's following The Zone -- he now weighs 800 pounds, but still can't stand on his own, and spends his days in a special industrial-size bed.

"I had an obesity problem for many years, a very significant one. I was gaining and gaining weight. I was on every diet you can imagine," Uribe said.

"I used to eat normal, just like all Mexicans do. … Beans, rice, flower tortilla, corn tortilla, French fries, hamburgers, subs and pizzas, whatever regular people eat. I worked as a technician, repairing typewriters, electronic calculators and computers. So I worked on a chair. It was a sedentary life," he said.

Uribe is beyond the kind of overweight that comes from fast food and lack of exercise. Doctors call it morbid obesity.

According to the National Institutes of Health, obesity means weighing 20 percent or more than your ideal body weight, and it's a health risk.

Morbid obesity is altogether different. Sometimes called "clinically severe obesity," it means you're 100 pounds or more over ideal body weight, with a body mass index of 40 or higher.

Uribe doesn't gain weight like the rest of us. Brain chemistry, genetic mutation, addiction, psychological pain -- or an unhappy combination of all of them -- makes morbid obesity one of the biggest mysteries of medicine.

Dr. Jaime Gonzalez makes house calls to Uribe once a week. His goal: to help his patient lose 1,000 pounds. Uribe's legs and lower body are massaged daily to improve blood circulation.

"Our main concern currently [are] his lower extremities," Gonzalez said. "There are large volumes because of the amount of fluids retained here."

Incredibly enough, in spite of his enormous weight, Uribe says he is in good health.

"Yes, I have accumulated fat, but I'm healthy," he said. "I don't have sugar, cholesterol, triglycerides, diabetes or high blood pressure. My heart works perfectly fine."

"We don't have an explanation," Gonzalez said.

New Yorker Michael Hebranko poses another medical mystery. Twenty years ago, at 1,100 pounds, he was considered the fattest man in the world. "I could eat two dozen eggs," Hebranko said. "Thirty-six pork chops, 24 frankfurters. I've eaten two dozen bagels at one time with two packages of cream cheese. I'm never full. I'm never, never, ever full."

Then, in the late 1980s, with the help of celebrity dieter and exercise coach Richard Simmons, Hebranko miraculously dropped from 1,100 pounds to 200 pounds -- in only 19 months.

He became an overnight success, appearing on a Simmons workout video and becoming a motivational speaker to the super obese.

"I'm in the Guinness Book of Records in 1990 as the world's greatest dieter. I lost the most weight in the shortest time," he said.

His success was short-lived, though. Flash-forward seven years, and Hebranko was back up to 1,000 pounds. At his worst, he was forklifted out of his apartment and rushed to the hospital.

Then, like Uribe, he spent the next three years of his life bedridden. "That was pretty much the worst part of my life," Hebranko said.

A Genetic Mutation?

Dr. Jeanine Albu of the New York Obesity Research Center at St. Luke's-Roosevelt Hospital has been Hebranko's doctor for the last 20 years.

"There's signals in his brain. The signals are telling him to eat, and they are never telling him when to stop," she said.

Scientists say the morbidly obese are radically different from the rest of us. A genetic mutation may be driving their appetites.

In one study, they narrowed the difference between fat mice and thin mice to a hormone in the brain called leptin. The mice without it were always hungry, always enormously fat. It's the "off switch" for eating. The fat mice didn't have it. A new study in The New England Journal of Medicine shows that only 3 percent of the obese people in the study have the disturbed leptin gene. Says Albu: "Could any one of us gain, to be 1,000 pounds? I don't believe so. I think most people would probably get sick, but there would have to have been something with Michael or people of this size that allows this to happen."

Some experts also call morbid obesity an addiction.

Marc Burd, Hebranko's therapist, has worked with addicts in prison.

"To me, the overeating is an addiction, and if you ask most of the patients. … The words or the symptoms that they describe when they get the cravings to eat is exactly the same thing you'll hear from any drug or alcohol [addict]," he said.

In 2003, Hebranko, weighing 769 pounds, entered the Brookhaven Rehabilitation and Health Care Center in Far Rockaway, N.Y., a home that treats morbidly obese patients.

He's currently on a 1,200 calorie-a-day diet to lose weight. He uses a ventilator at night because the pressure of his weight could stop his breathing.

When asked why he couldn't stop gaining weight, Hebranko told ABC's John Quinones: "It is a mystery. There's something inside of you, because not everybody can be 500 pounds. … I don't know how to stop it. I know that it needs to be controlled."

"I don't know if there is a way to stop it. … I'm pleading for the professionals out there to figure out. While me, the little guy, tries to fight it every day," he said.

In Mexico, Uribe deals with his weight loss. He doesn't want a gastric bypass. He's on the Zone diet -- a moderate program in carbs, protein and fat. No more rice and beans! Always by Uribe's side, his mother, Ofelia Uribe, prepares five meals a day.

"What do you want for your son?" Quinones asked.

"That he can get up and walk," a hopeful Ofelia Uribe said.