Albert Lasker
Clinical Medical Research Award

Award Presentation by Michael Brown

If you've ever used a hand-held pump to inflate a bicycle tire, you know that pumps need two valves—one to permit air to enter on the intake stroke, and the other to permit air to exit during expulsion. Our hearts are no different. Each of the two pumping chambers has two valves—one for intake and one for expulsion. Heart valves are remarkably resilient. Over a human lifetime they open and close 3 billion times, allowing 50 million gallons of blood to pass. When they close, they prevent the backflow of this deluge. It's no wonder that heart valves wear out. They can wear simply with age, or they can fail early in life as a result of birth defects, or diseases like rheumatic fever and bacterial infections. Disease can constrict the valve, blocking the flow of blood, or it can render the valve leaky, permitting devastating back-flow. Often a single valve can suffer both problems.

Before 1960, disease of heart valves meant certain death—either catastrophically or slowly when the heart failed as it tried to overcome the inefficiency in pumping blood. All of that changed on a single day—September 21, 1960—in a surgical suite in Portland, Oregon. There, Albert Starr implanted the first successful artificial heart valve in a 52-year-old man who was literally on his death bed. In childhood, this man had suffered from rheumatic fever, which had fatally damaged his mitral valve, the one that admits blood into the left ventricle. Earlier, surgeons had tried to repair the valve, but the valve was beyond repair. Without a new valve this man would surely die. Starr's artificial valve was a remarkable success and the man lived normally for 10 years until he was killed by falling off a ladder.

The story that led to this medical miracle began two years earlier when Lowell Edwards, a 62-year-old inventor with experience in fluid dynamics, walked into Starr's office and proposed the invention of an artificial heart valve. Starr was a young surgeon, fresh out of residency, who had trained at Columbia College of Physicians and Surgeons right here in New York. After further training at Johns Hopkins, in 1957 Starr moved to Portland to start a clinical and research program in the brand new field of open heart surgery. He took Edwards up on his challenge, and the two set out to invent a heart valve. For the next two years they experimented intensely on dogs. After trying other designs, they eventually chose a caged ball valve like one that was invented as a wine bottle stopper in France a century before. It didn't look like nature's solution, but it had two properties that made it ideal: First, it did not damage the blood cells as they passed through it; and second, it was partially resistant to clotting.

Starr and Edwards made careful calculations of the size of the opening and the physical and chemical properties necessary for the ball and its cage, and then they tested it by implantation into dog hearts. Their biggest problem was blood clotting. When blood touches a foreign surface it triggers a cascade of enzymes that quickly make the blood congeal. Clotting is essential to life. But it creates an enormous problem when one places a foreign object in the bloodstream. Fortunately, Starr and Edwards could take advantage of inventions made for other reasons. First, they made the ball from silastic, a combination of silicone and plastic invented by Dow Corning scientists in the 1940s as a sealant. When exposed to blood, silastic is relatively inert. Second, they could block clotting by using a new oral anticoagulant, coumadin, that had been invented 10 years earlier as a rat poison.

Of course, the very idea of heart valve replacement could not have been envisioned without the pioneering work of John Gibbon, who in 1953 performed the first open-heart surgery using a heart lung machine. Gibbon received the Lasker Award in 1968. The world also owes a debt to Charles Hufnagel, a surgeon who had earlier implanted a caged ball valve in the aorta of a patient with aortic regurgitation.

In addition to their creativity, skill and courage, Starr and Edwards are noteworthy for their unselfish efforts at teaching other surgeons how to duplicate their success, and their diligence at keeping track of their patients and reporting their failures as well as successes. By the present time, modifications of the original ball valve have been made, and new approaches have been pioneered, as we will hear in a moment. Nevertheless, it is proper to consider Albert Starr and Lowell Edwards as the fathers of artificial valves, and millions of patients literally owe their lives to them. Unfortunately, Lowell Edwards passed away in 1982. Otherwise, he would surely have shared today's Award.

The Starr-Edwards valve broke the ground, but it left a problem. The recipients were committed to taking anticoagulants for the rest of their lives. The dose must be adjusted carefully. If the dose is too low, clots form on the valve, triggering strokes and other catastrophes. If the dose is too high, blood will not clot and fatal bleeding will occur. Now the scene shifts to Paris and another young surgeon, Alain Carpentier. As a surgery resident in the early 1960s, Carpentier observed a young man who had received a Starr-Edwards valve and had suffered a stroke caused by a blood clot. Carpentier decided to devote himself to finding a valve that would not clot.

Previous work had shown that animal valves could be implanted into human hearts, and they did not clot. But there was a problem. After a few months the animal valves deteriorated. Through brilliant deduction Carpentier discovered that the valves would function much longer if they were first treated with glutaraldehyde, a chemical that crosslinks the proteins of the valves, reinforcing the structure much like bridges are supported by cross-linked triangular beams. Glutaraldehyde also reduces the tendency of the valve to stimulate immune rejection. Carpentier obtained valves from pigs, treated them with glutaraldehyde, and attached them to a ring that kept them expanded and allowed them to be sewn into the human heart. After this treatment the pig valve was no longer natural—it was a new structure that Carpentier called a bioprosthesis. The result was dramatic. Bioprosthetic valves are efficient and long-lasting. Moreover, the patients do not require anticoagulants. The valves work especially well in older patients.

Today, the majority of valves implanted into people above age 60 are Carpentier valves. But Carpentier did not stop with bioprostheses. He realized that sometimes the valve did not need to be replaced. He developed ingenious methods to reinforce and repair the patient's own valve. His repair methods revolutionized cardiac surgery.

Another of Alain Carpentier's contributions deserves recognition. He has used his skill, his influence and his personal wealth to bring the benefits of cardiac surgery to thousands of poor people in developing countries. In 1992, he founded a hospital in Vietnam that performs 1000 open heart surgeries every year. As a Director of the World Heart Foundation, Carpentier has brought the benefits of cardiac surgery to many nations in Africa. But Dr. Carpentier doesn't only help the poor. He saves some time for the rich. Last year he performed emergency surgery that saved the life of a prominent New Yorker, Charlie Rose, whose mitral valve failed while in Syria.

As I look back at the enormous contributions of Starr and Carpentier, I am struck by the confluence of prior advances that they brought together. Of course there was the heart-lung machine. But this machine could not have been invented without something as mundane as silastic tubing. Coumadin was a rat poison. Glutaraldehyde came from leather tanning and electron microscopy. And no surgical advance could take place without medical discoveries like antibiotics, methods to manage fluid and electrolytes, selection of blood donors who are compatible immunologically, and treatment of heart arrhythmias. Technology expands geometrically. Each advance multiplies the advances before it. We live on the ascending limb of this expansion where unrelated advances can be brought to bear on a single problem like valvular heart disease. And all of this happened before Google, the limitless library that allows every inventor immediate access to all prior knowledge. What a playground for creative minds like those of Starr, Edwards and Carpentier. Let us all act to insure that the human benefits from this age of enlightenment do not fall victim to those who would return the world to ignorant darkness.