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The Heparin DisasterFriday, July 4, 2008 THE HISTORY OF HEPARINScientists have long realized the need to deal with clotting when disturbing blood flow during dialysis or other procedures. In 1913, John Abel, a pharmacologist at Johns Hopkins University, reported the first successful performance of dialysis in a dog using “hirudin,” an anticoagulant extracted from leeches. (Mark J. Acierno, Vera Maeckelbergh “Continuous Renal Replacement Therapy,” Compendium, May 2008, Vol. 30, No. 5; Research Defence Society Website, “Anticoagulants,” (2008)). This early anticoagulant was unsuitable for human use, however, as it was expensive, difficult to extract and purify, and caused severe heart and lung problems, as well as allergic reactions. (Research Defence Society Website, “Anticoagulants.”) Heparin, one of the oldest drugs currently still in widespread clinical use, was discovered in 1916 by a second-year medical student, Jay McLean (1890-1957), and his Professor of Pharmacology, William Henry Howell (1860-1945) at Johns Hopkins University in Baltimore. (Wikipedia: Heparin; Rutty, Christopher, Health Heritage Research Services, “Miracle Blood Lubricant: Connaught and the Story of Heparin, 1928-1937.”) Allthough “the first description of heparin has been clouded in controversy,” it is reported that McLean, working under the direction of Howell, was investigating pro-coagulant preparations, when he isolated a fat-soluble phosphatide anti-coagulant from liver cells from dogs, (hence its name hepar or "ηπαρ," which is Greek for "liver"). (“Practical Haemodialysis Began with Cellophane and Heparin: The Crucial Role of William Thalhimer (1884-1961),” Nephrol. Dial. Transplant (200) 15: 1086-1091; Wikipedia: Heparin.) Although it appears that “Howell initially seemed not to have welcomed this discovery, perhaps because [he] disagreed with [McLean’s] theories of coagulation,” most historians believe that McLean’s work lead to Howell’s later isolation of a water-soluble polysaccharide anticoagulant in the early 1920s. (“Practical Haemodialysis Began with Cellophane and Heparin: The Crucial Role of William Thalhimer (1884-1961),” Nephrol. Dial. Transplant (200) 15: 1086-1091; Wikipedia: Heparin.) This early heparin, however, was expensive, toxic and not practically applied by doctors until the early 1930s when a research team lead by Dr. Charles H. Best at Connaught Medical Research Laboratories, (then part of the University of Toronoto), developed a method to make it into a “purified, plentiful and inexpensive supply safe for human use.” (Rutty, Christopher, Health Heritage Research Services, “Miracle Blood Lubricant: Connaught and the Story of Heparin, 1928-1937;” Wikipedia: Heparin.) In 1928, Best, the head of University of Toronto’s Physiology Department and an Associate Director of Connaught, “decided to break the heparin stalemate and explore its practical value.” (Rutty, Christopher, Health Heritage Research Services, “Miracle Blood Lubricant: Connaught and the Story of Heparin, 1928-1937.”) Best then expanded his team in 1929 to include Drs. Arthur F. Charles (1905-1972), an organic chemist, David A. Scott (1892-1971), a scientist closely involved with insulin production, and Dr. Gordon Murray (1896-1976), a prominent surgeon at Toronto General Hospital. (Id.) Charles and Scott turned to beef liver because it was cheaper than dog liver and readily available from local slaughterhouses. (Id.) When the price of beef liver increased, they turned to beef lung and intestines. (Id.) In conjunction with Murray’s experimental surgeries on animals using the more potent heparin, the team succeeded in purifying and then crystallizing heparin into a standardized dry form that could be administered in a salt solution. (Id.) In May of 1935, the first human trials began and “by 1937, it was clear that Connaught's heparin was a safe, easily-available, and effective blood anticoagulant.” (Wikipedia: Heparin.) FDA first approved heparin drug products for sale within the U.S. in the 1940s. (04/14/08 USP Press Release.) Labels: Abel, Baxter, Best, Charles, Connaught, Heparin, heparin attorney, heparin lawsuit, heparin lawyer, Heparin Timeline, Howell, Johns Hopkins, McLean, MDL, Murray, nightline, over sulfated chondroitin sulfate, Scientific Protein Labs, Scott |
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