Heparin a naturally occurring substances in many animals. It is an important drug to treat heart attacks and clots in our arteries and veins. We also use it when we want blood not to clot, and to keep it flowing through artificial conduits such as dialysis and vascular catheters. Discovery of heparin was also quite serendipitous. Further, its history intertwines with that of Insulin in more ways than one.
Jay McLean, had his share of struggles to become a doctor. Determined to enroll at John Hopkins medical school at Baltimore, he saved money for his expenses. In the year 1915, he also started working in the lab of Dr William Henry Howell, to gain some research experience. Dr Howell was an eminent physiologist, and he asked McLean to work on brain thromboplastin a substance that activates clots. It seems McLean extended his research to other tissues, one of these being liver. The substance from liver, turned out to be a clot-buster instead. Later this was named as “Heparin”, which means from the liver (hep=Liver).
While McLean went on to become a surgeon, Howell continued to work with heparin. Three years later, in 1918 he announced discovery of an anticoagulant, which he named heparin. It was still not used for human use, as it was still impure. Howell teamed with Charles Best to find ways on how to purify heparin. Meanwhile, Howell retired in 1931, and further development moved to Toronto, under supervision of Charles Best.
Meanwhile, in 1929 a Swedish Cardiothoracic surgeon Clarence Crafoord realized clinical utility of Heparin. He urged his colleague Erik Jorpes to work on this substance. Jorpes’s lab in Sweden was not only able to purify the substance, elucidate its structure, but also use it successfully in humans. Between 1935 and 1945, it was used in considerable number of patients to either prevent or treat blood clots.
Meanwhile, Howell died in 1945 and till that time was credited to be the sole discoverer of heparin. McLean claimed credit, only after Howells death, probably not to offend his mentor in his lifetime. Charles Best, played his role in supporting McLean in his claim. Discovery of heparin now belongs to Howell and McLean, quite like Banting and Best of insulin fame.
Interestingly heparin is found in a variety of organisms, including some that do-not have blood. It is also found in intestinal mucosa, liver and lungs. As a naturally occurring anti-coagulant it helps to keep blood flowing inside the blood vessels and tissues. It acts by binding to anti-thrombin, inhibiting the action of this naturally acting procoagulant in our blood.
This exact mechanism of action of heparin was discovered in 1970s, and so was effect of a heparin product, which we know of as LMWH (or low molecular weight heparin). Today most heparin is derived from hog (or porcine) intestine, and only little from other sources. Its more popular form, LMWH is a distillation product of naturally derived heparin. Nearly 100 tonnes of heparin are produced annually worldwide, from close to one billion hogs. Since most of it comes from China, quest is on to source it from other cattle or to artificially synthesize it.