How A Scientist's Slick Discovery Helped Save Preemies' Lives

Aug 3, 2015
Originally published on August 3, 2015 9:05 pm

In 1953, Dr. John Clements realized something fundamental about the way the lung functions — an insight that would ultimately save the lives of millions of premature babies.

The story begins in 1950, when the U.S. Army sent Clements, a newly graduated physician, to the medical division of what was then called the Army Chemical Center in Edgewood, Md. Clements was interested in doing research in biochemistry. His commanding officer was of a different mind.

" 'We don't need any biochemists,' " Clements recalls the officer saying. " 'You're going to be a physiologist.' And I became a physiologist because the Army said so."

At the time, the Army was worried about the Soviet Union using chemical weapons.

"My assignment was to find out how nerve gases worked on the lungs," says Clements. So he set out to learn all he could about human lungs.

Lungs are made up of thin, pliable sacs called alveoli. You can think of them as tiny, somewhat permeable balloons. Oxygen enters the bloodstream through the outer membranes of these sacs.

When the sacs inflate, there's more surface area for oxygen to cross into the blood.

But how much surface area is there in the normal lung? This wasn't an easy question to answer. Researchers who had looked at lung tissue through the microscope said the surface area was huge — maybe the size of a football field if you spread it all out.

But physiologists who estimated the energy that's used to inflate the sacs came up with a much, much smaller area.

"That huge discrepancy between two supposedly correct methods bothered me," Clements says.

In 1953, he suggested an explanation for the discrepancy. Maybe there was a substance in the lung that made the alveoli easier to inflate and keep inflated. A few years later, Clements and others found it — a slippery substance known as a surfactant that reduces surface tension in the alveolar membranes. Soon scientists showed that a lack of surfactant is involved in human lung disease.

"At that point the research, to use the trite term, exploded," Clements says.

Clements was doing basic research, not trying to cure a disease. But his work did contribute to a cure. In 1959, a researcher named Dr. Mary Ellen Avery, who was then at Harvard Medical School, showed that the lungs of premature babies can't make that surfactant. In those days, many children born at less than 37 weeks' gestation would die from something called respiratory distress syndrome, or RDS.

The FDA has since approved five synthetic surfactants to prevent respiratory distress syndrome in premature babies. Surfaxin, approved in 2012, is the latest to hit the market. (The first, Exosurf, is no longer sold.)

"It took 40 years — from the initial discovery in the early '50s to the first approval of the FDA in the 1990s," says Dr. Sam Hawgood, a neonatologist who once worked in Clements' lab and is now chancellor at the University of California, San Francisco.

"All of us would like to compress that timeline," Hawgood says. "But if you think that we had no idea that this substance even existed or was needed in the '50s, to an actual drug four decades later — it's pretty remarkable."

What's also remarkable is John Clements himself. Today he has a lab at UCSF. At 92, he still heads in every day and is proud of what his work has meant for treating premature infants with respiratory distress syndrome.

"When we began this work back in the 1950s, the mortality from RDS was above 90 percent," he says. "Today, that mortality is 5 percent or less."

I asked Clements why he still works — surely he's achieved enough to rest on his laurels. He says there's always the chance that a new day will bring a new scientific insight.

"The thrill of that is the best thing there is. At my age, I'd put it even higher than sex," says Clements with a laugh. Then his tone is more serious. "It's a big, big thrill when you think you've made a discovery — found an idea — that no one else has had," he says. "That's as good as it gets."

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Transcript

RENEE MONTAGNE, HOST:

Today in Your Health - most of the time, biomedical research advances in tiny increments. Still, every once in a while, a researcher makes a discovery that leads to a complete change in medical practice. As part of his series Joe's Big Idea, NPR's Joe Palca introduces us to a scientist who had a fundamental insight that ultimately saved the lives of millions of premature babies.

JOE PALCA, BYLINE: In 1950, the U.S. Army sent a young doctor by the name of John Clements to the medical division of the Army Chemical Center in Edgewood, Md. Clements was interested in doing research in biochemistry. His commanding officer was of a different mind.

JOHN CLEMENTS: We don't need any biochemists. You are going be a physiologist. And I became a physiologist because the Army said so.

PALCA: At the time, the Army was worried about the Soviet Union using chemical weapons.

CLEMENTS: My assignment was to find out how nerve gases worked on the lungs.

PALCA: So he set out to learn all he could about the lungs. Now, the lungs are made up of thin sacs called alveoli. Think of them as tiny balloons. Oxygen enters the bloodstream through the outer membranes of these sacs. When these sacs inflate, there's more surface area for oxygen to cross into the blood. But how much surface area is there in the normal lung? It's not an easy question to answer. One group of researchers made an estimate based on what they saw through the microscope. They calculated the surface area was huge, maybe the size of a football field if you spread it all out. But others tried estimating the size based on the energy needed to inflate the sacs. They came up with a much smaller area.

CLEMENTS: That huge discrepancy between two supposedly correct methods bothered me.

PALCA: Then in 1953, Clements discovered a way to explain the discrepancy. He said, what if there were some substance made in the lung that made it easier to inflate the alveoli? A few years later, Clements and others found that substance. Not long after that, another team of researchers showed it played a role in human lung disease.

CLEMENTS: At that point, the research - to use the trite term - exploded.

PALCA: Clements was doing basic research, not trying to cure a disease - but the work did cure a disease. Turns out that premature babies can't make that substance called lung surfactant. So without it, they frequently died from something called respiratory distress syndrome, or RDS. Sam Hawgood is chancellor of the University of California, San Francisco, but once upon a time, he worked in Clements' lab. Hawgood says there's now a synthetic form of surfactant for treating premature babies.

SAM HAWGOOD: It took 40 years from the initial discovery in the early '50s to the approval of the FDA in the 1990s, and all of us would like to compress that timeline. But if you think that we had no idea that this substance even existed or was needed in the '50s to an actual drug four decades later, it's pretty remarkable.

PALCA: What's also remarkable is John Clements himself. Today, Clements has a lab at the University of California, San Francisco. He's now 92, and he still goes in every day. He's justifiably proud of what his work has meant for infants with respiratory distress syndrome.

CLEMENTS: When we began this work back in the 1950s, the mortality from RDS was above 90 percent. Today, that mortality is 5 percent or less.

PALCA: That's about as big an improvement as you could possibly hope for in medicine. I asked Clements why was he still coming into the lab. I mean, surely he'd done enough at this point in his research career. He said the answer is there's always the chance that a new day will bring a new scientific insight.

CLEMENTS: The thrill of that is the best thing there is. Well, at my age, I'd put it even higher than sex (laughter). But it's a big, big thrill when you think you've made a discovery, found an idea that no one else has had. That's as good as it gets.

PALCA: Well, sounds good to me. Joe Palca, NPR News. Transcript provided by NPR, Copyright NPR.