Tiburon Dr. John A. Clements’ research revolutionized care for premature infants
Tiburon resident Dr. John A. Clements, a titan in the field of pulmonary biology whose research was revolutionary in treating respiratory distress syndrome in premature infants, died at his home Sept. 3. He was 101.
His death was announced Sept. 12 by the University of California at San Francisco, where Clements was a professor of pulmonary biology and pediatrics from 1960 to 2004, when he became a professor emeritus.
Clements is renowned in his field for his discovery of pulmonary surfactant, a soapy substance that helps make lungs easier to expand by reducing their surface tension. Along with his colleagues at UCSF, Clements developed an artificial surfactant that eventually led to the version that is used today in premature infants, allowing their air sacs to deflate without collapsing.
“His discovery of lung surfactant and subsequent work that created an artificial version of this vital substance have saved literally thousands of lives of premature infants and is widely regarded as the most important discovery in pulmonary physiology in the last 50 years,” wrote the Lasker Foundation in awarding Clements the 1994 Lasker-DeBakey Clinical Medical Research Award, which recognizes outstanding work in the diagnosis, prevention, treatment and cure of disease.
Pulmonary surfactants stabilize lungs’ air sacs, called alveoli, which allow for oxygen and carbon dioxide to exchange between the lungs and blood.
Clements’ early research career at what’s now the U.S. Army’s Edgewood Chemical Biological Center in Maryland focused on the effects of nerve gas on the lungs, and he questioned how lungs could exhale without collapsing, according to an obituary written by UCSF.
He theorized there must be something in the lungs that lowered the surface tension of the liquid covering the air sacs. He identified that substance as a surfactant and demonstrated its presence in the lungs in a 1956 paper based on his own research, according to an obituary published in the New York Times.
By 1959, Harvard University researcher Mary Ellen Avery and laboratory head Jeremiah “Jere” Mead published findings that pulmonary surfactants were missing in premature babies who died of infant respiratory distress syndrome.
Roughly 10,000 infants died annually of the syndrome in the 1960s, including Patrick Bouvier Kennedy, the second son of President John F. Kennedy and Jacqueline Kennedy. Patrick was born 5½ weeks early in August 1963 and died two days later.
After Clements’ discovery and Avery and Mead’s finding, scientists worked to develop synthetic surfactants, including Clements himself, who didn’t want to use animal byproducts in fear of easily triggering inflammatory responses.
“It sounds incredibly naïve, or maybe at the other pole, really arrogant, but I said, ‘Well, I’ll make one for you,’ trying to accomplish in a few weeks or months what had taken divine providence millions of years — if you believe in evolution,” Clements told UCSF’s media office in a 2017 career retrospective.
He developed artificial surfactant Exosurf for Burroughs Wellcome and Co., now part of multinational pharmaceutical company GlaxoSmithKline PLC, and received approval in 1990 from the Food and Drug Administration.
A series of clinical trials funded by the National Institutes of Health eventually determined that surfactants derived from animal lungs worked better, and those are used today.
Clements’ research and development of surfactants is credited with slashing infant mortality rates due to respiratory distress syndrome in the U.S.; the rate had fallen to about 414 in 2021, based on the Centers for Disease Control and Prevention’s National Center for Health Statistics rate of 11.3 deaths per 100,000 live births.
John Allen Clements was born March 16, 1923, to Harry Clements and May Porter in Auburn, New York, about 37 miles south of Lake Ontario, as the youngest of four children.
As a kid, Clements knew he wanted to be a scientist, gathering materials to build a Tesla coil with 15,000 volts. Both his parents were intellectuals — his mother “a proper Victorian lady” and his father a general-practice attorney, he said.
“It was obvious to me that my parents were pleased when I brought home good grades,” he told iBiology Science Stories in 2017.
Clements was his high school’s valedictorian and attended Cornell University, the only school he applied to. He completed both his bachelor’s and medical degrees in 5½ years, graduating from the Weill Cornell Graduate School of Medical Sciences in 1947.
He married classical music singer Margot S. Power, who performed with Marin Symphony Orchestra, in 1949, according to the New York Times obituary. Clements was himself an accomplished pianist who often accompanied her concerts, according to a 2008 Ark article. They had two daughters, Carol and Christine, who grew up in Tiburon’s Reedlands neighborhood, where the family lived beginning in 1961; both declined to be interviewed.
The same year he wed, Clements began working at the Army research center, supervising military-contracted research on lung physiology.
While there, Clements was assigned to work with the Harvard School of Public Health, where colleague Edward “Ted” Radford, one of the first scientists to correctly promote that radiation exposure greatly increases the risk of developing cancer, was conducting similar experiments to those of Swiss physician Kurt von Neergaard, who in the 1920s found lungs’ alveoli had a liquid lining and that surface tension adds to their elastic recoil. Radford was trying to estimate alveoli’s surface area.
But Radford’s experiments were only a tenth of what was previously calculated, Clements wrote in a 1997 perspective. When Clements asked Radford why, he told Clements, “Well, you wouldn’t understand it.”
“I’m usually a mild-mannered person, but that got under my skin,” he said. “And I thought, clenching my teeth, ‘I will understand this without your help.’”
Clements wrote he could see differences in air- and saline-filling pressures as lungs were emptied, and if airspaces weren’t increased, surface tension would have to fall with volume, leading to his hypothesis.
However, surface tension wasn’t taught to biologists and physicians back then, and he said he worried about whether his theory was right, or if he even understood it.
“We had to pull ourselves up by our bootstraps, reading the literature of surface chemistry and physics, finding virtually nobody to discuss it with, and trying to apply it to pulmonary physiology ourselves,” Clements wrote.
When Clements presented his findings in fall 1956, it was met with little reaction, and academic journal Science rejected his findings; they eventually got published in non-peer reviewed journal Proceedings of the Society for Experimental Biology and Medicine in 1957. Despite the article being in a “déclassé rag,” it became a “Citation Classic” by the Institute for Scientific Information, a forerunner to Clarivate’s Web of Science, he wrote in 1997.
Though artificial surfactants aren’t as necessary in treating premature babies today, UCSF Chancellor Sam Hawgood said in 2017 for Clements’ career retrospective that much of Clements’ research led to improved tools in obstetrics, including when university scientists helped develop continuous positive-airway-pressure treatments for vulnerable infants in the years before artificial surfactants became widely available.
“I was struck by his incredible humility and his unbelievable depth of knowledge of physics and physiology and lung function,” said Hawgood, who was also trained as a fellow alongside Clements. “He would guide me in the gentlest but cleverest way — to either see the faulty way of my thinking, or to encourage me to continue.”