NOVA

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Narrator

Troy Fryer has less than 2% body fat. Although he looks extremely fit, it's the lack of fat that makes his muscles stand out. With no padding on his face, his cheeks look sunken and his eyes are deeply set. -

Man

How far are you off that way? The little bit of fat on my body is behind my eyeballs and on my liver. So, walking around not having fat, it feels like constant needles are poking through the bottom of your shoe. You know, some of us stand up all day and we're okay with it, Troy is not because he has no padding on his feet, nothing in between his knees, there's no comfort at all. It's just unbelievable to watch him struggle. -

Narrator

Troy was born with a normal amount of fat. But by age six, he began rapidly losing weight, despite having a voracious appetite. I would go through two or three loaves of bread in one day, making 10 sandwiches at a time. So I would keep eating and eating and eating, until it would hurt if I didn't get that food out, get really upset and really angry, I would rip doors off their hinges. I actually sent him in for a psych evaluation thinking that there was something wrong because he couldn't take the answer no, it's like he was starving. -

Narrator

By age nine, Troy was clearly ill. Doctors were shocked to find that his blood was full of fat and cholesterol, symptoms typical of obesity. It made no sense until Troy was diagnosed with a genetic disease called lipodystrophy. We always think about thinness as something good. But in generalized lipodystrophy, it's beyond thinness. It's actually absolute lack of fat under the skin, so the excess energy doesn't have a place to go. -

Narrator

And that's why Troy was sick. With no fat tissue, excess calories collected in his liver, enlarging and inflaming it. And when it got to that point of the doctors saying, "There's nothing else we could do for you," Troy turned to the doctor and said, "So how and when am I gonna die?" -

Narrator

Salvation would come from the discovery of a mouse that also couldn't stop eating. But unlike Troy, this mouse was fat, not thin. A genetic mutant from a breeding experiment, it was nicknamed OB For obese. This mouse had a defect in a single gene. And the impact of that gene was a mouse that weighted three times normal and had five times as much fat. And it overate voraciously. Genetics is very powerful because what it tells you is that obesity has a biological basis. What that basis is required identifying the gene. -

Narrator

Scientists began to hunt for the mutation that made the mouse obese. Combing through the 2.5 billion letters of its genome. Think of this as an alphabet, you spell out letters of the genome, there are four letters A, G, T, and C. These spell out, indirectly, proteins and a single spelling error can lead to a defective gene. -

Narrator

In 1994, after a decade of work, Friedman and his collaborators homed in on a gene only found in fat cells. That was really the moment of a lifetime. I pulled out the film with some vague hope that maybe this would reveal something about the nature of the OB gene and I looked at it and in that instant, I knew that we had identified the gene that makes a hormone that plays a very active role in regulating appetite, metabolism and probably other biological systems. So if you injected that hormone into the blood of an OB mouse, the mouse lost weight, it would completely cure the mutation of an OB mouse. And over the course of a few weeks, depending on the dose you give, they'll look indistinguishable from a normal mouse. -

Narrator

The hormone was named leptin, from the Greek work Leptos, meaning thin. It's discovery transformed our view of fat and the biological forces controlling appetite. The OB mouse cannot see itself in a mirror and realize that it's hugely obese. It thinks it's starving to death because this very critical hormone is not being made by the body and the idea that a hormone, produced by fat, can control what you think about food in a very important way, this is a very radical notion. -

Narrator

A normal fat cell produces leptin, which travels to the brain and signals the hypothalamus, the region that determines when and how much we eat. High levels of leptin tell your brain you have plenty of fat stored. But low levels trigger an alarm to eat. And for those like Troy, who can't make leptin because they lack fat, getting the hormone would be lifesaving. The starvation was gone within three days of him taking leptin. We saved a lot of money (laughs), Troy went from eating what three people would eat to eating what a normal person would eat in a day. Knowing that I was full, I'm like wow, this is amazing. -

Woman

Does it hurt? -

Narrator

Leptin can't cure Troy's disease, but my curbing his hunger, it protects his liver. Leptin does not bring the fat back, it just helps to deal with fat's absence. Patients finally can take a deep breath that they're full and they don't have to worry about eating.