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Ozone is first mentioned in 1785 by Dutch chemist M. van Marum, but it was not until 1840 when German chemist C. F. Shönbein succeeded in synthesize it and described its relevant chemical properties.

In 1857, Werner von Siemens invented the dielectric barrier discharge (DBD), used later by Kleinmann to destroy microorganisms, and to perform the first insufflations in both humans and animals.

Medical use of ozone begins in World War I, between 1915 and 1918, when Dr. R. Wolf uses the gas to clean and disinfect wounds. In 1935, E. Payr points out how it helps the scar formation process, and in 1943, Dr. Albourg proposes rectal administration to treat intestinal and bladder infections. He also notices the rise in blood's oxidation potential.

In the early 70s, the Medical Society for Ozone application in Prevention and Therapy is founded to help launch ozone therapy and its application in several diseases. This therapeutic agent has been used for many years in countries such as Germany, Austria, France, Italy, Switzerland, Japan, the United States, Spain, Cuba, and many others.

Starting in 1981, ozone is used in Cuba to disinfect water and studies begin in the Centro Nacional de Investigaciones Científicas (CENIC) (National Centre for Scientific Research), the country´s most renowned scientific institute. The first Ozone Therapy Experimental Room is created in 1986 with the participation of multidisciplinary groups. In 1988, the first International Conference of Ozone Therapy is held in Cuba, bringing many countries together; in 1990, the First Iberoamerican Congress of Ozone Therapy; in 1992, the Ozone Research Centre is created from the CENIC's “Ozone Group”, that gathered 18 years of work experience developing research in that field.