Pioneers of Heparin
Dr. Murray would become one of Canada’s most famous cardiac surgeons, performing numerous congenital heart operations; though his career would end in controversy and isolation, when he announced a surgical cure for traumatic paraplegia that did not stand up to scrutiny. But the benefits from his early and innovative use of heparin are uncontested.
Apart from heparin’s clinical benefits in vascular surgery, the anticoagulant also proved to be an invaluable boon to the development of blood manipulation and analysis devices. In fact, before the days of Teflon tubing, heparin made possible the development of the first kidney dialysis machine when it was used to coat glass tubing to prevent coagulation. Heparinization also became key to preventing the formation of thrombus resulting from the implantation of artifical cardiovascular grafts—whether as blood vessels, patches, or heart valves.
It wasn’t until the mid-1970s and early 1980s that the true structure of heparin and its molecular mechanism were finally worked out by several research laboratories. Scientists such as Dr. Robert Rosenberg and Dr. Ulf Lindahl and their colleagues and competitors discovered that the molecule acts as a binding activator of the protease inhibitor known as antithrombin, enhancing its activity at preventing the coagulation cascade. Chemical synthesis of the components of heparin was reported by Dr. Pierre Sinay, Dr. Maurice Petitou and colleagues around 1984 and quickly other researchers worked out its biosynthetic pathway.
Today commercial, injectable heparin is still isolated from animals—in this case porcine intestinal mucosa. However, researchers at Rensselaer and the University of North Carolina at Chapel Hill, recently reported synthesizing hundreds of milligrams of heparin using engineered enzymes (J. Biol. Chem. 2005;280:42817-25).
BOXED QUOTE:
‘First it was necessary to determine the effect of the heparin . . . in the dogs which were to be used for the thrombosis test.. . . After three weeks of testing and as I was about to use a very large dose, I received a phone call from Dr. Best’s office to drop whatever I was doing and come over immediately. When I arrived, Dr. Best asked what I had been doing. I showed him my record book. He said "that’s all very well Jacques, but do realize you have used up the world’s supply of heparin?" ’
—L. B. Jacques, D.Sc., reflecting on his days as a student assistant with Dr. Best and Dr. Murray in the early days of heparin research (J. Ortho. Med. 1993;8:139-148).
More information
1. "Heparin: The Contributions of William Henry Howell" (Circulation 1984;69:1198-203).
2. "Preparation of Heparin and Its Use in the First Clinical Cases" (Circulation 1959;19:79-86).
3. "The Use of Heparin in Thrombosis" (Annals of Surgery 1938;108:163-77).
