Obituary for John Allen Clements, M.D., 1923–2024

Dr. John Allen Clements, a colossal figure in pulmonary research, died at his home in Tiburon, California, on 3 September 2024, at the age of 101. Dr. Clements' discovery of pulmonary surfactant and his invention of a synthetic surfactant have resulted in the saving of the lives of many thousands of prematurely born infants. John Clements was born on 16 March 1923, in Auburn, New York, the youngest of four children, to Harry and May Victoria Clements. As a child, John knew that he wanted to do research. At age 9, he made a sign that he hung in the front window of the family home that proclaimed in flashing red lights, “SCIENTIST.” Clements was an undergraduate and medical student at Cornell University. Under the US Army accelerated programme, he finished this formal education in 6 years. In 1949, after 2 years as a Research assistant in the Department of Physiology at Cornell Medical College, he joined the Army to satisfy his 2-year requirement and was assigned to the US Army Chemical Center in Edgewood, Maryland. At Edgewood, his initial project was to research the effects of nerve gas on the lung. As he learned more about lung physiology, he was intrigued by the marked differences in the calculated total surface area of the lung alveoli depending on the methods used. While studying this, he theorised that there must be a substance on the surface of the alveoli in the lung that lowers surface tension as alveoli decrease in size during exhalation. Otherwise, these small air sacs would collapse with each exhaled breath and thus prevent effective exchange of oxygen and carbon dioxide in the lung. He then did studies using a homemade modified Langmuir–Wilhelmy surface balance that could mimic the changes in size that the alveoli undergo during breathing. This work resulted in his 1957 classic paper demonstrating the presence of a surface-active material in the lungs [1]. At that time, the leading cause of death in newborns was the respiratory distress syndrome (RDS) that affected premature infants. RDS was originally known as atelectasis of the newborn because on radiograph, the lungs appeared atelectatic and at autopsy, the lungs were airless. In contrast, at autopsy the lungs of individuals who died from other causes contained air in the alveoli. Clements' paper stimulated the interest of Mary Ellen Avery, a paediatric research fellow at Harvard who was investigating why infants with RDS were dying. With Clements' advice, Avery and Jere Mead, a pulmonary physiologist, studied the lungs of infants who died from RDS. In their 1958 landmark paper, they reported that the lungs of infants who died from RDS were deficient in surfactant, and that was the cause of atelectasis and RDS [2]. This finding led to widespread intense efforts to develop a method of providing surfactant to premature infants. In 1961, Julius Comroe recruited Clements to the University of California San Francisco (UCSF) where he joined the Cardiovascular Research Institute and the Department of Paediatrics. Clements remained at UCSF for the rest of his career and was the leader of a productive pulmonary research group. In response to the need to obtain a surfactant to treat infants with RDS, Clements invented a synthetic surfactant, Exosurf, which he and his colleagues showed to be an effective treatment for RDS [3]. Exosurf was the first exogenous surfactant licensed by the US Food and Drug Administration and was used in more than 50 countries. Subsequently, animal-derived surfactants have been shown to be more effective and Exosurf is no longer used. In recognition of his research contributions, Clements received many national and international awards. Most notable was the 1994 Albert Lasker Clinical Medical Research Award which states, ‘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’ [4]. Clements was held in the highest regard by his colleagues, who regarded John as a friend as well as an associate at work. Over the years, dozens of trainees studied in his laboratory. His office door was always open to provide advice, encouragement and assistance to faculty and trainees. One would go to him with what seemed a simple research question and would leave with much more insight into the subject. After Clements retired in 2004, he continued to go to UCSF three times a week into his mid-nineties to be available for consultation. In 1949, Clements married Margot Power, a classical singer. John was a skilled pianist and often accompanied Margot on the piano when she sang for friends. John and Margot were married for 73 years until her death in 2022. They are survived by their daughters, Christine and Carol.