"I was stunned to learn that we had received this year’s award," says Zapol. "I regard myself as a clinician-scientist rather than an inventor. But I can certainly see why they chose to recognize inhaled nitric oxide. It has saved the lives of thousands of blue babies and others with pulmonary hypertension in this country and around the world, which has been rewarding enough for me." Zapol is the Reginald Jenney Professor of Anesthesia at Harvard Medical School.
The award will be announced June 4 at a 9:30 a.m. press conference at the National Press Club in Washington. Rep. Howard Berman of the House Subcommittee on Courts, the Internet, and Intellectual Property will present the award at a Capitol Hill reception Wednesday evening. Among previous recipients of the award are Paul Macready for the "Gossamer Condor" human-powered flying device, Robert Jarvik for the Jarvik Seven Artificial Heart, James L. Fergason for liquid crystal displays, and Amar G. Bose for a folded waveguide loudspeaker system.
For many years nitric oxide (NO) gas – not to be confused with the anesthetic nitrous oxide – was considered a dangerous pollutant. Then in the mid-1980s three US researchers discovered that the body naturally used NO to transmit key signals in the pulmonary, cardiovascular and other systems. Those scientists – one of whom was a former MGH resident – received the 1998 Nobel Prize in Medicine or Physiology for their discovery.
Subsequent NO studies showed that among its many functions was to relax the muscles surrounding blood vessels and reduce blood pressure. Because many serious medical conditions are characterized by constriction of blood vessels in the lungs, Zapol and several colleagues at the MGH began to study its potential as a treatment. As a gas, NO had a key advantage over other medications available at the time. Those intravenous drugs reduced blood pressure throughout the body, but the MGH researchers discovered that inhaled NO only relaxes blood vessels in the lungs.
Zapol worked with Frostell, who at the time was a postdoctoral research fellow at MGH, to develop a system to continuously administer a low concentration of NO in oxygen. Once this equipment was perfected, animal studies showed that inhaled NO opened only constricted lung vessels and had no effect on vessels that were normal. "Claes was a bright, enthusiastic student who saw a wonderful opportunity to test a new molecule that turned out to be powerful and useful," Zapol says. "He helped our research enormously."
The first clinical application studied at the MGH was treatment of a rare, potentially fatal disease in infants – persistent pulmonary hypertension of the newborn (PPHN). In this condition, the blood vessels in newborns' lungs do not expand as they usually do soon after birth. Several MGH studies led by Jesse Roberts, MD, showed that inhaled NO could rapidly and effectively treat PPHN, turning babies that were blue from lack of oxygen a healthy pink in a matter of minutes.
In 1999 the US Food and Drug Administration approved inhaled NO for the treatment of PPHN and other hypoxic respiratory failure in newborns. The treatment is also used to improve lung circulation in infants after surgery for congenital heart disease and to help diagnose pulmonary hypertension in adults. Ongoing NO research at the MGH and other centers includes investigating its use in infants with a condition called pulmonary vascular disease and to treat painful sickle cell crisis. The treatment devised by Zapol and Frostell is currently licensed to INO Therapeutics, Inc., a subsidiary of AGA-Linde Corp., which markets it under the brand name INOmax.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $350 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women’s Hospital joined to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups, and nonacute and home health services.