The Story of the Family that Couldn't Sleep

This is TALK OF THE NATION: SCIENCE FRIDAY. I am Ira Flatow.

A bit later in the hour, a mathematical mystery. But first up, a medical mystery. A new book tells the tale of an Italian family suffering from a rare and deadly disease called fatal familial insomnia. Just like it says, it's insomnia, an illness that literally kills its victim by robbing them of the ability to sleep. They die of exhaustion. You know how you say I'm just so tired I could die. These people actually die of exhaustion.

The disease is linked by the new science of prions to outbreaks of the neurological disease kuru in Papua New Guinea in the 1950s, and mad cow disease in the UK in the last decade. So we're going to start this hour by talking about the family that could not sleep and the strange protein called the prion. And if you'd like to join our discussion, our number is 1-800-989-8255, 1-800-989-TALK.

D.T. Max is a science writer and the author of The Family That Couldn't Sleep: A Medical Mystery. He's written for The New York Times and the New Yorker, and he joins us today from our NPR studios in Washington. Welcome to the program.

Mr. D.T. MAX (Author, The Family That Couldn't Sleep): Thanks very much.

FLATOW: This sounds like a really unusual disease. They really die because they can't sleep.

Mr. MAX: That's essentially right. It's a disease, fatal familial insomnia. The name sort of puts it all on the table. It's a progressive, inherited condition, characterized by eventually a total insomnia - leading within about nine months time to death.

FLATOW: So you're awake - you're dying when you're awake because you can't sleep?

Mr. MAX: Yeah, I think that's one way to look at it. We don't really know. One of the reasons I was drawn to this project to begin with is really the question of why we sleep. And in fact, we still don't really know why we sleep. But paradoxically, we know we have to sleep.

And in the case of this family - much for the same reasons that we have this paradox I've just laid out - this family cannot sleep and they ultimately die - and therefore we believe they die from a lack of sleep. There are other causative problems. They lose the ability to regulate their autonomic systems - their sweating, and their pupils become these tiny little pinpricks. I mean many things happen to them. It's almost a kind of a plane crash of a disease, and yet they have a complete insomnia that's clearly one of the key symptoms and one of the causes of the death.

FLATOW: And you say this is probably the worst disease in the world because of people suffering from it are aware they're awake, about what's happening to them.

Mr. MAX: That's right. I mean I would always be reluctant to rank diseases in terms of horribleness, but I think a case certainly could be made that this disease in many ways - one, because of this insomnia - and anyone who's ever, you know, suffered insomnia knows just how dreadful a condition it is...

FLATOW: Right, right.

Mr. MAX: ...even if the insomnia is simply worries about work tomorrow.

FLATOW: Sure.

Mr. MAX: You stay awake and the clock ticks and the clock ticks. But while this disease has much in common with Alzheimer's in terms of some of the things going on physiologically in the brain, what makes it quite different from Alzheimer's is that you - is that many, many of the sufferers of the disease have the ability to understand exactly what's going on. And even to be in, you know, routine verbal contact with their loved ones at the end, even though they've had this extraordinary insomnia.

FLATOW: You say there are about 40 families in the world known to have this disease.

Mr. MAX: Yeah, that would be a bit of a guess. We have 40 families based on the genomes that we know, and we can extrapolate from that that probably there would be maybe around 200 families worldwide. And I would emphasize that these - this disease, which is a mutation, of course - that these 200 families would all have developed the mutation probably separately.

FLATOW: Hmm. And you trace - it's interesting - in the book you trace the disease through several generations of an Italian family. One of the most memorable cases was a man named Silvano. Tell us about him.

Mr. MAX: Well, Silvano was a member of the family in the 1980s. And Silvano - the disease as far as I could trace it back - and I had the assistance of the family in digging through records.

In Italy, records are kept - these sorts of records are still kept in the parish houses of the churches, because the Catholic church was once responsible for recording births and deaths. And so the way they would assemble - the family would assemble information on its ancestors was, you know, you'd have to go into the church, and you'd have to ask for the records. But in Italy, records aren't really freely available. So there's a figure in the book named Ignazio - who's a young doctor who marries into the family and who - Ignazio's very much responsible for helping to solve the mystery of fatal familial insomnia.

Ignazio was an organist. He was an ardent Catholic in the Italian fashion, which means that he really - as he used to love to say to me - I believe because it's absurd.

(Soundbite of laughter)

Mr. MAX: So Ignazio is also an avid organist and very talented. And Ignazio would go into the church and he would ask the priest could he go and, you know, play the organ. And the priest would say sure, and Ignazio would play for a little while, and then the priest would get bored and go back into the parish house. You know, in Italy, priests have really quite nice parish houses, and they have someone who looks after them, so it's kind of its own life.

And then when Ignazio noticed that the priest was no longer listening, he would sneak down into the basement where the parish records were taken - were kept - and he would take photographs of anyone who had the same last name as his wife's family.

So with his help, I was able to trace the disease back to the 1760s, in all probability to a doctor, fascinatingly enough, who probably - I doubt he was the first member of the family, but he might well have been. You know, it could also have gone back further. But when you get before the Napoleonic era, you pretty much lose records in Italy because of the devastation of the Napoleonic Wars.

In any event, fast-forward to Silvano; we're in the 1980s. And, you know, Italy had become very rich in the period from the end of the Second World War to the 1980s, and Silvano was very much a product of the new Italy. He was a stunningly handsome man who loved to go out at night. I don't think I've ever seen a picture of Silvano not wearing a tuxedo.

So this was a man who, from the way I look at things, would probably not have been well-equipped to deal with a devastating disease, just because he was, again, to my mind, a man who very much judged by exteriors. He was a very external man. But he was also the head of the family - which in Italy is a very potent post - and he had just watched two of his sisters die from this unnamed, familial disease of which clearly had an important insomnia component.

So Silvano, in his heart, always knew, I think, that he would get the disease. And one thing we haven't mentioned that we should, is that the disease strikes in your 50s. So you get - one reason the disease doesn't burn itself out, the way of many severe genetic mutations, is because you live long enough to reproduce...

FLATOW: Right.

Mr. MAX: ...so it foils that mechanism, so to say, by which most diseases are - most really virulent genetic diseases are eliminated.

Silvano one day, in the Italian style, was dancing with his mother. And in Italy, you know, young bachelors are always dancing with their mothers, even today. And so he noticed he was sweating, which he knew from his experience with sisters was the first sign of the disease. And so Silvano understood what was happening. He'd always really known, I think, that he was going to get the disease. And then he went and looked in the mirror and he saw that his pupils had become these tiny pinpricks, and he knew for sure what was happening.

And rather than just say, OK, I'm going to give up, I'm going to die, he really decided that he was going to throw everything he had, all of his strength, into trying to understand what was killing his family. And so he went to a neurological institute in Bologna, with the help of Ignazio - this young man who had married into the family - and he basically said to them - he sat down with a young neurologist who really just graduated from, you know, graduated shortly before and had done his neurology residency.

And the neurologists will tell me, you know, what seems to be the problem? And so Silvano says - you know, this is obviously taking place in Italian - he says I know how I'm going to die. It's exactly the way that my father died and my two sisters have died, and I can give you all the details.

And the neurologist was stunned, because you know, neurologists are trained in the art of euphemism. They don't really have much to offer, but they do their best. And so the neurologist said, you know, please, please, sir, you know, we have cures, we have palliatives. And Silvano said - he said, cut the nonsense, I assume when I'm gone you'll want the brain. That was Silvano. He was able to confront what was going to happen with great courage. And through the experience, through the extensive EEGs that were taken of his brain - because really nobody had done a proper EEG before on any of these people. EEGs were traditionally done in little snapshots. You know, what the family - what you needed to diagnose this family was to leave in an EEG in place for an hour, and then you would see that the brainwaves looked like nothing we had in the literature.

And you know, Silvano eventually, he died, and - but what had been learned from him, that this disease - that insomnia wasn't just a byproduct of this disease, but a key component of the disease. We really owe this to Silvano, although, you know, at that point there was still much, much left to be discovered about the disease. But it was the first step. It was the first step beyond saying we have a familial encephalitis, which was the typical diagnosis, you know...

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