Ten years later Hagedorn and Jensen discovered that injection of insulin would have a prolonged effect if mixed with protamine-rich salmon sperm. The necessity of a pH of 7 for activation made the handling of insulin difficult. Zinc was added to the mix as a stabilizer. By 1946, an easier-to-use crystallized form was developed, and it was marketed by 1950 as NPH insulin.
When a patient is overdosed with heparin, excessive bleeding can be a problem. Protamine sulfate is a valuable medication used for reversal of heparin. Protamine is a strongly basic substance that combines with the strongly acidic heparin to form a stable complex. The protamine-heparin complex is not an anticoagulant; protamine causes a dissociation of the heparin-antithrombin III complex, resulting in loss of heparin’s anticoagulant activity. Given too quickly it may cause hypotension or anaphylaxis and may cause allergic reactions to patients with fish hypersensitivity.
From the anticoagulant effect of salmon sperm, we move to the world of Annelida. More than any other creature, the leech stands out as the epitome of biotherapy. Its name alone, Hirudo medicinalis, emphasizes its medical nature. Used by many ancient societies, the leech reached its zenith in mid-19th century France. Leeches were the fashion, women’s dresses were decorated with faux leeches, and cosmetics were applied to give that “healthy pale look” sometimes attained by being bled with leeches.
In 1833 more than 40 million leeches were imported into France. However, the leech’s days were numbered. The biggest blow was when Pierre Louis made his name as the father of medical statistics by proving leeches led to a worse outcome in treating pneumonia. The death of the leech was the birth of evidence-based medicine.
But all is not lost for the leech lover. The use of the leech as an anticoagulant was recognized in 1884. In its modern chemical form, recombinant leech saliva marketed under names such as lepirudin, is indicated for coronary thrombolysis, unstable angina hemodialysis, heparin-induced thrombocytopenia, and DVT prophylaxis. Recombinant hirudin, a man-made chemical similar to leech saliva, is manufactured in large quantities and is much easier to obtain than “milking” leeches. The mechanism of action is direct inhibition of thrombin. Leeches are making a comeback in the treatment of skin grafts, however. A mechanical leech has also been designed.
The argument for the protection of our planet’s biodiversity could not be more obvious. A new treatment for diabetes comes from Gila monsters. What novel substances lurk in the ever-shrinking rain forests? Whether from lizard or leech, the day of biotherapy is not yet done. Despite all this, I’m not cornering the market on synthetic eye of newt. TH
Jamie Newman, MD, FACP, is the physician editor of The Hospitalist, consultant, Hospital Internal Medicine, and assistant professor of internal medicine and medical history, Mayo Clinic College of Medicine, Rochester, Minn.