John Clements, MD, has been an emeritus UC San Francisco professor since 2004, but don’t expect him to be available to meet without his first checking his still-busy calendar.
When you call, he might be working on a study of surface tension in the lungs, the culmination of many years’ research that may shed new light on how tiny particles that are common air pollutants are eventually expelled from the lung’s lower airways.
Clements, age 93, is a giant in the field of pulmonary biology, renowned for discoveries leading to the effective treatment of premature infants born with underdeveloped lungs that cannot take in life-giving oxygen.
Lung surface tension has long fascinated Clements, and his early exploration of it well over half a century ago led him to first predict the existence of a vital substance called surfactant – and then to eventually make an artificial version.
Surfactant is a kind of soapy lubricant that allows lungs to expand. Premature infants born too early have not yet begun to make it, so the relatively rapid commercialization of Clements’ version was a game changer in neonatal intensive care units. Before artificial surfactants became available, “respiratory distress syndrome” was the leading cause of neonatal death in the United States.
Now, at an age when most others would be retired, Clements is still exploring his research field and pushing for others to carry on his work.
Fateful Assignment Led to His Research
Clements’ lung research odyssey began with fate, but was driven by curiosity. As a student he first favored chemistry and enjoyed physics, but finally turned to medicine.
In 1949, after completing accelerated Army-supported medical training at Cornell University, Clements volunteered for service at the Medical Laboratories of the Army Chemical Center in Maryland. His college thesis adviser had gone there before him, and Clements thought they could work together on biochemical problems.
Instead, his commanding officer told him, “You’re a physiologist,” and set him to work investigating how to protect lungs from nerve gas, a Cold War-era research concern. Clements found himself supervising Army-contracted research by leading lung physiologists at Harvard University. His background reading in his new field and his unwillingness to ignore a discrepancy in their study of lung surface tension piqued his curiosity and led him to the idea that something in the lungs must be altering surface tension as they expand and contract with each breath.
Clements determined through experimentation that there is in fact a substance in lung extracts that lowers surface tension in the lungs and prevents air sacs from collapsing. His groundbreaking paper on surfactant was initially rejected by the leading journal Science, but it eventually garnered the recognition it deserved, and more researchers entered the field. It came to be understood that lack of surfactant was killing premature infants.
In 1959, Julius Comroe, MD, the head of the new Cardiovascular Research Institute at UCSF, and a mover and shaker who drew talent and funding, persuaded Clements to move west. Clements began teaching pulmonologists how to do research in his new lab – among the first was William Tooley, MD, who a few years later founded the neonatal intensive care unit at UCSF – and Clements’ contributions to the understanding of the role of surfactant during development continued.
Development That Saved Lives
At the end of the 1970s, extract from cow lungs was tried as a treatment in human newborns with respiratory distress syndrome, with some success. As Clements recounts, “People in the intensive care nursery at UCSF asked me, ‘What treatment should we try here?’” Clements did not want to use an animal-derived extract that might easily trigger 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 succeeded, and U.S. Food and Drug Administration approval for the artificial surfactant came in 1990, leading to thousands of lives saved.
In 1994, Clements won the highly prestigious Albert Lasker Clinical Medical Research Award for what was “widely regarded as the most important discovery in pulmonary physiology in the last 50 years,” according to the award citation.
The treatment of prematurity has advanced in many ways over the past two decades, and Clements noted that artificial surfactant is less often needed than it once was.
However, as pointed out by UCSF Chancellor Sam Hawgood, MBBS, who trained as a fellow with Clements at the start of his career, “Many of the tools used by obstetricians to improve treatment were developed from knowledge contributed by John through his research.”
The use of glucocorticoids to speed maturation of the lungs and the secretion of surfactant stemmed indirectly from Clements' contributions.
Clements’ discoveries in lung mechanics also led UCSF anesthesiologist George Gregory, MD, along with Tooley, neonatologists Roderic Phibbs, MD, and Joseph Kitterman, MD, and others, to develop another life-saving treatment for the most vulnerable infants, called continuous positive airway pressure (CPAP). With CPAP, air supplied through tubes provided pressure needed to keep the immature lungs of distressed neonates from collapsing. The technique quickly spread worldwide.
But Clements enormous impact on a generation of scientists goes beyond reshaping scientific understanding of the lungs, Hawgood says, recalling his fellowship.
“I was struck by his incredible humility and his unbelievable depth of knowledge of physics and physiology and lung function. 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.”
“He also is well known for a wicked sense of humor,” Hawgood added.
Importance of Interdisciplinary Work
Others who trained with Clements also advanced to major academic leadership positions in the U.S. and abroad. But Clements himself would have viewed any academic leadership role as a distraction from his focus on the pursuit and thrill of scientific discovery.
“At my age, I can say it – it’s better than sex,” he says.
Clements credits his training in sciences beyond biology as being important to his success. In a perspective published two decades ago in the Annual Review of Physiology, he wrote, “Every time scientists are forced to look outside their disciplines, such cross-fertilization of minds can happen. The consequences are often unexpected, and sometimes wonderful.”
This is part of what is appealing about being at UCSF, according to Clements. “There is a lot of interdisciplinary work, and people help one another in ways that go beyond what is acknowledged in research papers.”
Curiosity and the thrill of discovery still drive Clements, but today he spreads his curiosity around. He loves to read – with favorite topics including molecular biology, quantum physics and history. He is an accomplished pianist and maintains his lifelong passion for music, one he shares with his wife, Margot, 91. They met young when she was starting her career as a professional singer of opera and Bach, and over the years they have performed together frequently. They still are able to live independently in their own home, but “We need each other more often for ordinary things,” Clements says.
Clements continues to meet regularly with his research colleagues, friends who also live in Marin, one retired, and one still seeing patients. “It’s no longer publish or perish, but we think it’s important work, want to get it out there, and hope someone else will pick up on it and carry it on.”
As Clements once wrote, “A field plays out only when our imagination fails and we can no longer think of good questions to ask.”
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