“I started paying attention,” Ringer said, “and I came back to him and said, ‘I’m reading these papers in genetics, like a baby with a novel form of something or other or a baby with a particular enzyme deficiency. I don’t get [why I’m bored with clinical genetics]. I’m reading all of these genetics papers.’ ”
“No, you idiot,” the friend responded. “You’re reading articles about babies.”
Never a slouch during college and medical school, but not at the top of his class either, Ringer found residency to be more suited to his temperament. In an environment marked by grinding days and nights, sick children, anxious parents, and unpredictable colleagues and supervisors, Ringer stood out. He had gifted hands and a way with people; in a high-stress atmosphere, these were critical skills. By the time he chose neonatology, his reputation had grown, and every training program wanted him.
The previous year, Ringer had done a summer research elective in a lab at the Marine Biological Laboratory on Cape Cod, working with the sperm and eggs from sea anemones. It was a plum assignment and in a place where his young family could spend a month at the beach in lab-subsidized housing. The lab was a side interest of Bill Speck, chief executive officer of the pediatric hospital in Cleveland where Ringer was a resident, and Speck would visit once or twice each summer to check on his research.
The following summer, as Ringer was deciding which fellowship to take, he returned to Speck’s lab on Cape Cod. Unseasonably warm oceans had interrupted the sea anemones’ gamete production, and when Speck visited, Ringer had to tell him that there was nothing to research at the moment. Speck had just bought a boat, and so while they waited for the anemones to spawn, the two Cleveland doctors—one an amiable resident, the other the CEO of the hospital—took the boat out and tried to figure out how to catch a striper, which, based on conversations they’d overheard at the dock, was the fish to catch. (Once they caught a bluefish—a dark-fleshed, strong-tasting fish not particularly appreciated outside of New England—and assumed that the dark lines along its glistening skin must be the stripes they’d been in search of. It took the smirks at the dock to disabuse them of the pride that they had caught a striped bass.)
While they sat in the boat under the bright summer sun, they got to talking, and Ringer heard amazing tales of infighting and political maneuvering at the highest levels of the hospital. To the young and impressionable Ringer, hospital administration seemed fascinating and even glamorous.
Ringer moved back to Boston and began a fellowship at Harvard’s Joint Program in Neonatology, an intellectually rich program that linked the academic resources of Harvard Medical School with clinical training in several of the most prestigious Boston hospitals, including Brigham and Women’s. In 1988, when Ringer and Ellie moved into a small home in Needham, the next town over from his boyhood home, neonatal medicine was enjoying the start of an arc of innovation that bent steeply up.
Sporadic attempts to sustain the lives of babies born too early dot the history of medicine. In the 1880s, the first incubator, designed to help premature newborns maintain their body temperature and modeled on warmers for poultry eggs, was developed, and a few years later, a French physician reported success with a flexible tube inserted in the nose that allowed milk to be delivered directly to the baby’s stomach.1
The oddest chapter in the history of neonatology started in the 1890s, when premature newborns, typically born six to ten weeks early and weighing between two and three pounds, began to appear at expositions across Europe inside the newly invented incubators. People flocked to see these marvels of science sustained in strange, glass-enclosed contraptions. By the early 1900s, these incubator-baby exhibits were regularly featured at state fairs and science demonstrations in the United States; a permanent display at Coney Island in New York lasted until the late 1930s. Rigorous statistics were not kept, but medical lore has it that the incubators increased survival for these babies to about 75 percent (most of them would have died otherwise). Once the babies reached a normal birth weight, they went home.2
Aside from that innovation, and subsequent spectacle, prematurity was one of those unavoidable and largely untreatable problems. If a baby was too small to breathe and couldn’t digest milk or formula, there was little the pediatricians could do. Perhaps because of the futility of treating it, prematurity was not a high-profile problem; this meant that for decades, any young academic physician seeking to make a name for himself chose to focus on curing cancer or pioneering lifesaving surgeries, not saving babies born weeks too early. Special units for premature newborns were established at a few hospitals, including the Children’s Hospital of Philadelphia—future surgeon general of the United States Dr. C. Everett Koop established a NICU there in 1962—but at most hospitals, premature newborns were placed in the pediatric intensive care units alongside youngsters with asthma, burns, head injuries, and other life-threatening injuries and illnesses.
The birth and death of Patrick Bouvier Kennedy changed that. The youngest son of President Kennedy, Patrick was born by cesarean section on August 7, 1963, at thirty-four and a half weeks, weighing nearly five pounds. Although today this degree of prematurity would be trivial, Patrick developed respiratory distress syndrome soon after his birth and was transferred from the air force base in Bourne, Massachusetts, where he was born, to Children’s Hospital Boston.
Overnight, the medical system’s limitations in caring for premature newborns were starkly revealed.
Robert Levine, considered to be an expert in premature infants at the time, was walking his dog outside his apartment on Central Park West in New York City when a police car pulled up beside him and an officer told him to get in. Levine asked why and was informed that the president needed him. He was taken by helicopter to Boston, but he was able to offer practically nothing other than consolation.
Maria Delivoria-Papadopoulos, a Greek pediatrician training in neonatology in Toronto, had modified an adult ventilator for use in preterm newborns, and months earlier she had published a paper describing how she had saved the life of a thirty-four-week baby girl who had developed lung disease shortly after birth. Desperate, the doctors at Children’s Hospital contacted Delivoria-Papadopoulos’s supervisor at the Hospital for Sick Children in Toronto and discussed flying Patrick Kennedy to Canada for treatment, but ultimately this was ruled out due to political considerations.
Without any other options, the staff at Children’s Hospital Boston put Patrick in a hyperbaric oxygen chamber—the same apparatus used for burn patients and divers with the bends—but to no avail. He died on August 9.
Levine, who had come to Boston in his pajamas and an overcoat, had to borrow money from a friend so he could buy a train ticket back to New York.
More than any new technology had, this death motivated pediatricians. Over the next few years, intensive care units designed specifically for newborns—full-term and preterm—sprung up at hospitals with large delivery volumes.
Now discoveries in newborn medicine came rapidly, as researchers examined the way each organ failed to function prior to the completion of development. Feeding presented two challenges: swallowing and digesting. Swallowing is a complex mechanical operation requiring the coordinating of mouth, tongue, and throat musculature to move liquid from mouth to esophagus without allowing it to enter the lungs. Although there are exceptions, many babies can’t master bottle- or breast-feeding until they are around thirty-four weeks of gestational age.
A simple way around this was tube feeding, pioneered as early as the 1890s, in which a tube was passed through the baby’s nose and down the esophagus, avoiding the problem of swallowing altogether and allowing nutrition to be dripped into the stomach.
This approach was lifesaving for newborns that could not yet swallow, but it still relied on the intestines to function normally. Most basically, the job of the intestines is to digest food into soluble proteins, carbohydrates, and f
ats and move them into the bloodstream, where the nutrients are transported throughout the body. Severely premature newborns could often be coaxed to digest milk or formula, but the process was slow and painstaking, and at a time when babies needed to gain weight fast, their intestines were notoriously unpredictable. Pediatricians had to bypass the intestines; they needed a predigested form of nutrition that could be infused directly into blood vessels. This seemed straightforward enough, but a host of obstacles complicated the development of this relatively intuitive technology.
Researchers created cocktails of carbohydrates and proteins and infused them into research subjects’ veins, only to find that the solutions were so concentrated they caused chemical injuries that obliterated the veins.
Next, investigators diluted their solutions with large volumes of saline in order to protect the veins and still get the nutrition into the patient. Reports in the 1940s and 1950s described adult patients infused with five to seven liters of fluid, causing nearly constant urination.
The breakthrough came in the 1950s with the discovery that if one advanced a catheter into a major vein at the center of the body—the vena cava, near the right atrium of the heart, became a favored location—the large volume of blood rushing through diluted the nutritional infusion and prevented injury to the blood vessels. This discovery allowed doctors to infuse concentrated solutions that provided sufficient calories for survival; the massive volumes of fluid that had been used in earlier years were no longer needed.
The first babies to receive intravenous feeding solutions in this way—called total parenteral nutrition, or TPN—were those born with gastroschisis, a relatively common condition in which the abdominal wall fails to form completely and the baby is born with its intestines exposed. These babies, who were in every other way normal, had been making it through the surgery required to close their abdomens but then dying of malnutrition before their intestines woke up and started functioning normally after their intestines had been replaced surgically inside their abdomen. (In babies, as in adults, the intestines often temporarily stop working when irritated by surgery or any other noxious stimulus.)
The use of TPN in newborns with gastroschisis turned a condition that had been almost uniformly lethal into one that was nearly always survivable. Over the course of a few short years in the 1960s, the death rate for babies with gastroschisis dropped from more than 75 percent to less than 5 percent.
It didn’t take long for the pediatricians to realize that TPN could also be used to help extremely premature newborns gain weight and grow. And as the TPN solutions became more sophisticated and more “lifelike,” the complications of using a substitute nutrition—liver failure and infection were the two most common—became less frequent.
Other discoveries were less dramatic. Humidified incubators helped regulate premature babies’ body temperature and limited fluid losses through their semitranslucent skin. (When one unit director in South Africa couldn’t afford incubators for his NICU, he turned the thermostat up to body temperature—98.6 degrees—and allowed the staff to come to work in shorts and T-shirts.) During these years, miniaturization of adult technology—from ventilators to catheters—provided pediatricians with equipment for the specific needs of their tiny patients.
Another major discovery, this one outside of the NICU, was that giving women in preterm labor steroid injections substantially reduced lung disease and brain injury in their premature infants. These injections became widespread beginning in the 1980s and 1990s, and those babies who were lucky enough to be exposed to the steroids while still in utero did much better after they were born than those who weren’t.
Perhaps the most important innovation in the care of premature newborns began with a 1959 discovery by a young pediatrician with an interest in prematurity. She’d been told to go learn about the foam that frothed from the mouths of adults with pulmonary edema, a lung disease usually resulting from heart failure, and so by day Mary Ellen “Mel” Avery, who would later become the top doctor at Children’s Hospital Boston, studied adults who foamed at the mouth. By night, to supplement her meager research stipend, Avery took care of babies born at the Boston Lying-In Hospital. Curiosity led Avery to search for a link between adults with pulmonary edema and preterm babies with lung disease, and the Lying-In gave her access to autopsy specimens of babies who had died of lung disease. What she found was startling: in those premature newborns, the tiny air sacs that were surrounded by blood vessels at the periphery of the lung had collapsed. Because the air sacs in the lungs didn’t stay open, the critical exchange of oxygen and carbon dioxide didn’t take place, and the babies essentially suffocated. Avery discovered that the babies’ lungs were collapsing because the surface tension holding the damp air sacs closed was insurmountable.
To understand what surface tension is, try this: First, lift a dry paper towel off a tile floor; you’ll notice that it comes up easily. Next, soak the towel in water, spread it on the floor, and try to pick it up. The “stickiness” between the damp towel and the floor is surface tension, and the same mechanism causes the damp walls of tiny air sacs to stick together. In a 1959 paper, Avery demonstrated that the surface tension in the lungs of premature babies who had died of lung disease was more than three times higher than the surface tension in the lungs of babies who had died of other causes. She speculated that babies with lung disease lacked some substance that reduced the lungs’ surface tension and prevented them from collapsing. The search was on for surfactant—the word comes from a contraction of “surface-active substance”—which is a natural product of the lung tissue in full-term babies.
At first no one believed Avery. “Mel’s playing with soap bubbles again” was something she heard repeatedly. But in the 1970s, her research began to come together: the composition of surfactant was worked out, the lung cells that made it were identified, and the specific effect the substance had on the lung tissue was demonstrated. (It turned out that the foam coming from the mouths of adults with pulmonary edema was full of surfactant.)
Avery teamed up with Japanese researcher Tetsuro Fujiwara, and, in 1980, an article announcing their research findings was published in the Lancet. A picture conveyed whatever their words did not. The researchers instilled surfactant into one lung and took an X-ray, and that X-ray is reproduced in the journal article: one lung is inflated, and the other is collapsed.3
It took until 1991 to get animal surfactant approved for use in premature newborns.
“It was an incredibly exciting time,” remembered Michael Epstein, who preceded Ringer as the director of the Brigham and Women’s NICU. “The innovations and discoveries came very fast.”
There were errors as well. Focused on lung disease and the problem of getting oxygen to these newborns, doctors had taken advantage of new incubators that allowed for the delivery of much higher oxygen concentrations to the babies. They didn’t spend a lot of time wondering why babies with lung disease were more likely to go blind from retinopathy of prematurity than babies without lung disease. It wasn’t until the 1990s that they realized that retinopathy of prematurity was caused by too much oxygen, and that premature babies thrived optimally on oxygen levels much lower than the levels required by full-term babies and adults. When they realized this, doctors started dialing down the oxygen concentrations, and they were dismayed to see the incidence of cerebral palsy rise as the reduced oxygen levels caused brain damage. Nuance was required, and babies suffered the consequences of the new field’s evolving science.
But during this generally golden era of newborn medicine, from 1963 until the mid-1990s, the death rate for premature newborns dropped fast. One study drawing on data from 1958 to 1968, the early era of neonatology, reported that the mortality rate for babies born at twenty-eight weeks was 70 percent.4 By 1988, when Ringer arrived in Boston, the mortality rate for babies born at this gestational age had fallen to 10 percent.
From his vanta
ge point in Cleveland, Ringer thought the Harvard Joint Program in Neonatology looked perfect. He could gain clinical skills at the three great NICUs that made up the program, and he would have an entrée into the robust research community at Harvard. Ringer felt confident that he could launch his research career in that environment.
What Ringer didn’t realize was that newborn medicine at the Harvard hospitals was chaotic. Physicians rotated from hospital to hospital, each of them bringing his own “very best” way to care for sick newborns. And because the field was so new, there wasn’t a body of medical evidence to point physicians in the right direction. Ventilator settings were arbitrary, infections were common, surgeons came and whisked babies off to the operating room without explaining why.
The nurses—who did not rotate among hospitals—were left to sort out the disorder and try to maintain consistency. Animosity developed: nurses did their best to defend the babies from the decisions of the transient physicians, and the physicians did their best to bring what they believed was the most optimal care to the babies.
At Brigham and Women’s, hospital administrators had the brilliant idea of putting the NICU in the basement. Physicians who worked there remember having to lean over the secretaries’ desks in the reception area and crane their necks upward toward the single skylight to see if it was snowing or raining, or whether darkness had fallen. The babies may not have minded the lack of windows, but the location added to the dysfunctional working environment.
Ignorant of the chaos as a trainee, Ringer found a lab that was studying the function of white blood cells, and he settled in to grow his career as an academic researcher and neonatologist.
Amid the babies, Ringer knew he had made the right choice. In his oversize beefy fingers, intravenous catheters found their way into the tiniest of veins, and breathing tubes reached just the right spots in the tracheas of the smallest premature newborns. He had an intuitive sense for the babies and quickly developed a feel for which of them would thrive and which would not. The nurses, a generally skeptical lot, trusted Ringer. They made him cookies, they laughed at his jokes (which were sometimes even funny), and they came to him to arbitrate conflicts.
Fragile Beginnings Page 5
