Albert Lasker
Clinical Medical Research Award

Acceptance Remarks by Alain Carpentier

Progress in medicine is often triggered by emotional circumstances. As a resident in cardiac surgery in the early 1960s at the Hôpital Broussais in Paris, I was struck by an artist suffering from a valvular disease whose valve had been replaced by a valvular prosthesis. Three months after the operation, he presented with a severe brain damage due to the migration of a clot formed in the contact of the prosthesis. He couldn't paint anymore. The same valve, which had saved his life, had now definitely impaired his quality of life. At this very moment, I decided to devote my research to this problem.

But how to start? Which direction to take? I knew that valves removed from human bodies and grafted to a patient did not produce clot formation. Unfortunately, this solution was complex in its implementation because of problems of procurement and infection. Valves retrieved from animals shouldn't have these disadvantages. Unfortunately, pig valves implanted in sheep were destroyed in a few days or weeks by acute immunological response. Something had to be done to prevent it. This required a much better expertise in immunology and chemistry than the one I had acquired during my medical education.

Although I was already an active cardiac surgeon, I persuaded with difficulty my chief, Professor Dubost, that I should spend one or two days a week at the Faculty of Sciences. At the same time, I developed my own research laboratory, actually a single small room in the basement of a building of my faculty. Exploring all chemical techniques of tissue fixation, I was fortunate to discover that glutaraldehyde could reduce the immunological response enough for the valve not to be rejected.

In research, more challenging than an idea itself, application requires favourable circumstances and some luck. I was lucky in 1969 to receive the visit, in my laboratory in Paris, of the famous surgeon Albert Starr. He was so surprised by my results that he advised me to develop this new valve in collaboration with the laboratory which was already manufacturing his own prosthesis. Using the engineering capacities of Edwards laboratories, the glutaraldehyde-treated pig valve was mounted into a stent to facilitate its surgical implantation in a human. I called it "bioprosthesis" to refer to its biological origin and its prosthetic fate.

The first implantation of a valvular bioprosthesis took place in May 1968 in Paris during one of the most famous revolutions of students. The operation succeeded, the revolution faded. Several other successful operations followed with the advantage for the patients not to be obliged to take any blood thinner. A 25-year old marathon runner wanted an additional advantage: "I want a bioprosthesis," he told me, "but can't you make it from antelope tissues?"—Why?—"Because antelopes run faster than pigs!"

The clinical results had been gratifying for six years when an unexpected complication emerged in patients younger than 60 years of age: tissue calcification that compromised long-term valve function. I returned to the lab and, with the help of my wife, Sophie, I improved the method of glutaraldehyde fixation by adding calcium-mitigating adjuncts. In the same time, I improved the valve design to minimize flow turbulence, an additional cause of calcification. These improvements almost doubled the durability of the bioprosthesis and extended the indications to younger patients. A lot of research work, however, remains to be done in order for this valve to be used in children. This is what I am doing now.

This prestigious award is the highlight of my career and a strong incentive to persevere, thus continuing to follow the St Augustine's motto which has influenced my whole spiritual and scientific life: "Always search, and when you have found, search again." Merci beaucoup to the Lasker Foundation and to its Jury.