Of all the cases Barbara Warner has faced as a pediatrician specializing in newborns, the one that sticks hardest in her mind involved a couple who had been trying for years to have children. Finally, in 1997, the woman was pregnant. She was in her mid-40s. “This was her last chance,” says Warner. Then, too soon, she gave birth to twins. The first child died at two weeks of respiratory failure, at the time the most common killer of preterm babies.
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A week later—it happened to be Thanksgiving Day—Warner folded down the blanket on the surviving twin, and even now she draws in her breath at the memory. The baby’s belly was reddened, shining and so swollen “you could have bounced a nickel off it.”
It was necrotizing enterocolitis, or NEC, little known outside neonatal intensive care units, but dreaded there as a sudden, fast-moving bacterial inflammation of the gut. On the operating table, a surgeon opened the baby boy’s abdomen and immediately closed it again. The intestinal tract from stomach to rectum was already dead. Warner, in tears, returned the child to die in the arms of his shattered parents.
“It’s 15 years later, and there’s nothing new,” Warner says bleakly as she moves among her tiny patients, each one covered in tubes and bathed in soft violet light, in a clear plastic incubator. NEC is still one of the leading killers of preterm babies. But that may soon change, thanks to a startling new way of looking at who we are and how we live.
Over the past few years, advances in genetic technology have opened a window into the amazingly populous and powerful world of microbial life in and around the human body—the normal community of bacteria, fungi and viruses that makes up what scientists call the microbiome. It’s Big Science, involving vast international research partnerships, leading edge DNA sequencing technology and datasets on a scale to make supercomputers cringe. It also promises the biggest turnaround in medical thinking in 150 years, replacing the single-minded focus on microbes as the enemy with a broader view that they are also our essential allies.
The subject matter is both humble and intimate. In Warner’s neonatal care unit at St. Louis Children’s Hospital, researchers studying NEC have analyzed every diaper of almost every very low-weight baby delivered there over the past three years. They don’t expect to find a single pathogen, some killer virus or bacteria, the way medical discovery typically happened in the past. Instead, says Phillip Tarr, a Washington University pediatric gastroenterologist who collaborates with Warner, they want to understand the back-and-forth among hundreds of microbial types in the newborn’s gut—to recognize when things go out of balance. Their goal is to identify the precise changes that put a baby on track to developing NEC and, for the first time, give neonatal care units crucial advance warning.
A separate research group demonstrated early this year that secretions from certain beneficial microbes seem to relieve the deadly inflammation characteristic of NEC. So doctors may soon see into life-or-death processes that until now have been hidden, and take action to address them.
The new insights into NEC suggest why the microbiome suddenly seems so important to almost everything in the medical and biological worlds, even our understanding of what it means to be human. We tend to think that we are exclusively a product of our own cells, upwards of ten trillion of them. But the microbes we harbor add another 100 trillion cells into the mix. The creature we admire in the mirror every morning is thus about 10 percent human by cell count. By weight, the picture looks prettier (for once): Altogether an average adult’s commensal microbes weigh about three pounds, roughly as much as the human brain. And while our 21,000 or so human genes help make us who we are, our resident microbes possess another eight million or so genes, many of which collaborate behind the scenes handling food, tinkering with the immune system, turning human genes on and off, and otherwise helping us function. John Donne said “no man is an island,” and Jefferson Airplane said “He’s a peninsula,” but it now looks like he’s actually a metropolis.
The modern microbiome era started in the late 1990s, when David Relman, an infectious disease physician at Stanford University, decided to get a sample of the microbes in his own mouth. It’s a simple process: A dentist scrapes a sort of elongated Q-tip across the outer surface of a tooth, or the gums, or the inside of a cheek. These samples typically look like nothing at all. (“You have to have a lot of faith in the invisible,” one dentistry professor advises.)