Sunday, November 30, 2008

Sudden Death, Explained

Recently, while reading the esteemed journal Science, I learned about a compelling new theory regarding the cause of Sudden Infant Death Syndrome (SIDS). As a physician, I am intrigued by SIDS because it is a mysterious medical phenomenon, but I also have a very personal interest in the problem.

As a boy, long before I took any of my pre-medical courses, I experienced the brutal reality of SIDS. Our neighbor found her six-month-old son – my friend Michelle's younger brother – dead in his crib. I was seven-years-old at the time and, despite my parents’ best efforts to explain what had happened, I was severely shaken. How could a healthy baby just die in his sleep, without any warning? Could that happen to me? Or my brother? I remember Michelle’s mother, a single parent, was puffy-eyed for months afterwards. Over the subsequent years, her house fell into disrepair and eventually, she and Michelle moved away. Since then, I have often wondered whether either of them ever recovered. And, I’ve followed each development in the SIDS mystery with interest. Babies have gone “Back to Sleep,” pollutants (including cigarette smoke and “stale air”) have been implicated, and so have excessive swaddling and hidden infections. Heart rate and breathing (apnea) monitors have been recommended and their utility subsequently disputed. Pacifiers and fans are in; mom and dad's bed is out. And still, in this country, over 2,000 infants die of SIDS each year.

Now, scientists are buzzing about the recent article in Science. “The exciting thing,” says Dartmouth physiologist Eugenie Nattie, “is that the mice are dying, spontaneously.” Watching mice die spontaneously may not seem all that exciting to you, but when you’re dealing with a devastating condition like SIDS, you can’t blame a physiologist for her morbid enthusiasm. The new evidence comes from an Italian experiment that found that mice who died spontaneously had out-of-whack serotonin levels. Serotonin is a mood-related brain hormone, one that can already be modulated by numerous pharmaceuticals (including prescription drugs such as anti-depressants and recreational ones such as ecstasy.) The Italian researchers, who set out to establish a model of the serotonin-feedback mechanism by injecting genetically modified serotonin receptors into mice, found, accidentally, that mice with decreased serotonin levels were at risk for sudden death – usually in conjunction with sudden and extreme drops in temperature or heart rate. The nature of this type of sudden death – in otherwise healthy mice – is very similar to what is believe to happen in human victims of SIDS. These results support previous human autopsy findings from 2006, which found fewer brainstem serotonin receptors in children who died from SIDS. Taken together, these studies provide a working model for how SIDS kills: infants with abnormal serotonin regulating systems are unable to effectively compensate for metabolic abnormalities (likely related to carbon dioxide levels) that occur during sleep.

The Italian team's unexpected findings can be added to a long list of serendipitous medical discoveries. Throughout human history, the science of medicine has advanced haphazardly. As Ben Gordon writes in The Alarming History of Medicine, “The history of medicine is largely the substitution of ignorance by fallacies.” And when truth has emerged, it has often been by chance. Antony Leeuwenhoek, a 17th-century Dutch draper, discovered the existence of microbes, “animalcules” he called them, after being inspired to examine his own semen under a homemade microscope. One of the greatest discoveries of the early 20th century, an antibiotic called penicillin, came about because microbiologist Alexander Fleming happened to go on a two-week vacation to the country. While Fleming was on holiday, his bacteria-filled Petri dishes became overgrown with a mold, pencillium notatum. When he returned, he observed that the areas around the mold were devoid of bacteria, and this gave him an extraordinary idea.

In the case of SIDS, it's not yet clear how the fortuitous new findings will alter prevention efforts. Ultimately, they may lead to the development of a genetic test to identify babies at high risk of SIDS. In the meantime, current recommendations (including pacifiers, circulating air, and “Back to Sleep”) are still very relevant. One thing, though, is for sure, this study should provide a touch of solace to the families of SIDS victims. I hope that Michelle’s mom, wherever she is, is one of those who can take heart. I hope she realizes that science seems to have found an explanation for what happened to her son – an explanation based on a genetic disorder. I hope that if she harbored any maternal guilt over all these years, if she suffered from any second-guessing and wondering… I hope she can now let those things go.