Invention: Helping newborn babies breathe
The invention of pulmonary surfactants by Swedish laboratory physician Tore Curstedt at Karolinska Institutet in Stockholm marked a milestone in saving the lives of early-born infants suffering from respiratory distress syndrome (RDS), a lung condition that was the leading cause of death among newborns for decades.
First introduced in 1989 in preliminary medical testing, the inventor's treatment consists of administering a protective coating to infants' lungs via a tube in the throat (tracheal intubation). The coating is a naturally occurring, slippery substance known as a "surfactant" that is derived from the lungs of pigs, and prevents the tiny, delicate sacs in the lungs - the alveoli - from collapsing. Now a standard treatment for infants born roughly three to ten weeks prematurely and suffering from RDS, Curstedt's invention has helped revolutionise treatment outcomes and has been administered to over 3 million newborns to date.
Curstedt and co-inventor Bengt Robertson (1935-2008) achieved their breakthrough by relying on the natural properties of surfactants to maintain surface tension in lung tissues. This also required a new approach to manufacturing the agent - chemical name "poractant alfa" - on a large scale because one pig lung yielded only enough surfactant for treating two newborns. Translational research efforts found support from Italian pharmaceutical company Chiesi Farmaceutici, which launched the drug under the name Curosurf - a combination of the words Curstedt, Robertson and surfactant.
As late as the 1950s and 1960s, infant mortality from RDS, then the leading cause of death in newborns, was as high as 90%. In fact, it was the death of the youngest child of US President John F. Kennedy and First Lady Jacqueline Kennedy to RDS just two days after his premature birth that helped spark interest in finding a cure.
These days, roughly one in eight births in the US and about one in fourteen births in Europe occur preterm according to the National Center for Health and EFONI respectively. However, thanks to the invention and the wide-spread availability of other surfactant treatments, the tables have turned dramatically. As of 2015, mortality rates for RDS have dropped below 5% in the developed world.
Preterm newborns suffering from lung complications now enjoy an unprecedented level of care. Clinical studies have shown that treatment with surfactant reduces mortality and any form of pulmonary air leaks in infants with RDS by about 30% and 50% respectively.
Approved for use in Europe in 1992 and by the US FDA in 1999, Curosurf has been used to treat over 3 million newborns with lung conditions, and is now available in 80 countries. Moreover, the drug is now administered routinely as preventive care to all infants under 30 weeks' gestation (10 weeks premature) needing intubation. The drug has been a stellar market success. In 2014, Chiesi reported EUR 175 million in sales from Curosurf, representing a 73% global market share with availability in over 80 countries worldwide.
Reporting total revenues of EUR 1.34 billion in 2014, family-owned Chiesi Farmaceutici is a major European player in pharmaceutical development, with an annual R&D investment of EUR 237 million. In a recent study, premature infants with neonatal RDS had a nearly 20% better chance of survival when treated with Curosurf compared to the two major competing surfactant therapies. Third-party analysts at MarketsandMarkets estimate the market for neonatal preterm infant care (equipment, drugs and formulae) in the US at EUR 13.04 billion in 2015. A separate study looking only at European neonatal care equipment predicts this market to reach EUR 1.51 billion (USD 1.79 billion) by 2019, at a CAGR of 8.33% (Mordor Intelligence).
Tore Curstedt in his lab
Bottle of porcine surfactant
Tore Curstedt in his lab
Tore Curstedt in front of Karolinska Institutet
How it works
The root cause of RDS was first documented as early as 1959 by Mary Ellen Avery and Jere Mead at the Harvard School of Public Health. The disease occurs when preterm infants lack the surfactants in their lungs that normally reduce the surface tension of the alveoli and prevent pulmonary collapse. Over the next decade, the challenge for researchers consisted of finding an alternative that mimicked the same properties of "sticking" to the surface of the lungs but enabling air to "slide off". Finally, Curstedt resorted to a naturally occurring equivalent, the poractant alfa found in the lungs of pigs.
Poractant alfa belongs to a group of chemicals known as phospholipids, fatty acids with unique characteristics in contact with water. While conventional fat cells are known for repelling water, phospholipids have a two-sided effect: one side can bind to water, for instance on the surface of cells inside the lung, while the other side - the lipid side - repels water, thereby working as a protective layer on surfaces inside the body, such as the lungs. Administered through a breathing tube inserted into the trachea, Curstedt's surfactants coat the lung membranes of preterm infants, reducing surface tension and preventing RDS.
As a young researcher at the Karolinska Institutet's laboratory, Curstedt began experimenting with surfactants to treat lung disease in the mid-1970s. In the process, he became one of the world's foremost experts in the isolation, separation and identification of phospholipids, which proved the basis for his breakthrough discovery.
During a career as a laboratory physician spanning over 40 years, Curstedt has published about 200 original articles, more than 30 review articles and several book chapters. Retired since 2013 from his position as the assistant director heading the Karolinska University Laboratory, Curstedt is currently engaged in final clinical trials for bringing to market a cost-effective synthetic surfactant, manufactured entirely without animal products. Currently known by its working name CHF5633, the drug is expected to enter the market in 2019.
For his pioneering efforts in reducing infant mortality, Curstedt has received numerous awards, including the Swedish Heart-Lung Foundation's Lars Werkö Prize (2004; jointly with Bengt Robertson) and the Chiesi Prize for Excellence in Neonatology (2011).
Did you know?
The discovery of surfactants is a fascinating story highlighting the interplay between medicine and physics. Through years of study, Mary Ellen Avery and Jere Mead further developed findings by physiologist John Clements to discover that the tiny and delicate alveoli sacs in the human lungs are able to retain their shape thanks to reduced surface tension. Much like soap bubbles, where the soap reduces the pressure differential between the inside and the outside of the bubble, alveoli would collapse in the absence of surfactant, with their surface tension becoming too high.
Putting the science of bubble popping into physical terms, a principle known as the Young-Laplace equation, helps explain the maximum size a bubble can be without popping. The same principle helps researchers determine the reduced surface tension necessary for properly functioning alveoli in babies (and adults).