Discovered in the late-1970s, the pioneering drug ivermectin, a dihydro derivative of avermectin—originating solely from a single microorganism isolated at the Kitasato Intitute, Tokyo, Japan from Japanese soil—has had an immeasurably beneficial impact in improving the lives and welfare of billions of people throughout the world. Originally introduced as a veterinary drug, it kills a wide range of internal and external parasites in commercial livestock and companion animals. It was quickly discovered to be ideal in combating two of the world’s most devastating and disfiguring diseases which have plagued the world’s poor throughout the tropics for centuries. It is now being used free-of-charge as the sole tool in campaigns to eliminate both diseases globally. It has also been used to successfully overcome several other human diseases and new uses for it are continually being found. This paper looks in depth at the events surrounding ivermectin’s passage from being a huge success in Animal Health into its widespread use in humans, a development which has led many to describe it as a “wonder” drug.
Over the past decade, the global scientific community have begun to recognize the unmatched value of an extraordinary drug, ivermectin, that originates from a single microbe unearthed from soil in Japan. Work on ivermectin has seen its discoverer, Satoshi Ōmura, of Tokyo's prestigious Kitasato Institute, receive the 2014 Gairdner Global Health Award and the 2015 Nobel Prize in Physiology or Medicine, which he shared with a collaborating partner in the discovery and development of the drug, William Campbell of Merck & Co. Incorporated. Today, ivermectin is continuing to surprise and excite scientists, offering more and more promise to help improve global public health by treating a diverse range of diseases, with its unexpected potential as an antibacterial, antiviral and anti-cancer agent being particularly extraordinary.
Since its introduction more than 20 years ago, ivermectin has proved to be one of the most successful therapeutic drugs in veterinary medicine, as well as the basis of one of the most successful public-health programmes of the past century. The drug arose from a unique international collaboration between the public and private sectors. The development process also incorporated the world's first and largest drug-donation programme and involved a unique association between governments, non-governmental organizations and industry. The drug is now being used, free of charge, in two global disease-elimination programmes that are benefiting millions of the world's poorest people.
A regional programme to combat lymphatic filariasis in the Pacific islands is showing great promise as it reaches its halfway point. The Pacific Programme to Eliminate Lymphatic Filariasis (PacELF), established in 1999, aims to eliminate the disease from the Pacific by 2010 - ten years ahead of the global target. Set up with support from Australia, and now funded primarily by Japan and underpinned by the Word Health Organization, PacELF is providing evidence that Pacific nations can work cooperatively to rid the region of one of its worst scourges, in addition to discovering techniques and new tools that should be of use in other regions.
Staurosporine, together with such examples as penicillin, aspirin, ivermectin and sildenafil, exemplifies the role that serendipity has in drug discovery and why 'finding things without actually searching for them' retains a prominent role in drug discovery. Hitherto not clinically useful, due to its potency and promiscuity, new delivery technology is opening up new horizons for what was previously just the parent compound of innovative, highly-successful anti-cancer agents.
Lactacystin exemplifies the role that serendipity plays in drug discovery and why “finding things without actually looking for them” retains such a pivotal role in the search for the useful properties of chemicals. The first proteasome inhibitor discovered, lactacystin stimulated new possibilities in cancer control. New and innovative uses are regularly being found for lactacystin, including as a model to study dementia, while new formulations and delivery systems may facilitate its use clinically as an anticancer agent. All this provides yet more evidence that we need a comprehensive, collaborative and coordinated programme to fully investigate all new and existing chemical compounds, especially those of microbial origin. We need to do so in order to avoid failing to detect and successfully exploit unsought yet potentially life-saving or extremely advantageous properties of microbial metabolites.
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