Vanes team found that one of the venoms peptides selectively inhibited the action of angiotensin-converting enzyme (ACE), which was thought to function in blood pressure regulation; the snake venom functions by severely depressing blood pressure. During the 1970s, ACE was found to elevate blood pressure by controlling the release of water and salts from the kidneys. Captopril, an analog of the snake venoms ACE-inhibiting peptide, was first synthesized in 1975 by three researchers at the U.S. drug company E.R. Squibb & Sons Pharmaceuticals (now Bristol-Myers Squibb): Miguel Ondetti, Bernard Rubin, and David Cushman. Squibb filed for U.S. patent protection on the drug in February 1976, which was granted in September 1977, and captopril was approved for medical use in 1980. It was the first ACE inhibitor developed and was considered a breakthrough both because of its mechanism of action and also because of the development process. In the 1980s, Vane received the Nobel prize and was knighted for his work and Ferreira received the National Order of Scientific Merit from Brazil. The development of captopril was among the earliest successes of the revolutionary concept of ligand-based drug design. The renin–angiotensin–aldosterone system had been extensively studied in the mid-20th century, and this system presented several opportune targets in the development of novel treatments for hypertension. The first two targets that were attempted were renin and ACE. Captopril was the culmination of efforts by Squibbs laboratories to develop an ACE inhibitor.
Maggot therapy – also known as maggot debridement therapy (MDT), larval therapy, larva therapy, or larvae therapy – is the intentional introduction by a health care practitioner of live, disinfected green bottle fly maggots into the non-healing skin and soft tissue wounds of a human or other animal for the purpose of selectively cleaning out only the necrotic tissue within a wound in order to promote healing.Although maggot therapy has been used in the US for the past 80 years, it was approved by the FDA as a medical device only in 2004 (along with leeches). Maggots were the first live organism to be marketed in the US according to FDA regulations, and are approved for treating neuropathic (diabetic) foot ulcers, pressure ulcers, venous stasis ulcers, and traumatic and post-surgical wounds that are unresponsive to conventional therapies. Maggots were used in medicine before this time, but were not federally regulated. In 1990, California internist Ronald Sherman began treating patients with maggots produced at his lab at the UC Irvine School of Medicine. Sherman went on to co-found Monarch Labs in 2005, which UC Irvine contracted to produce maggots for Shermans own continuing clinical research on myiasis at the university. Monarch Labs also sells maggots to hospitals and other medical practices, the first US commercial supplier to do so since the last one closed in 1935.In the US, demand for these fly larvae doubled after the FDA ruling. Maggot therapy is now used in more than 300 sites across the country.