The True Origin: A Microbe in the Soil
Contrary to common misconceptions that it might be an herbal or plant-based remedy, the natural source of ivermectin is a microorganism [1.2.1, 1.2.3]. The journey of this remarkable drug began in the 1970s when Japanese microbiologist Satoshi Ōmura, while hunting for new antibacterial compounds, isolated a new bacterial species from a soil sample collected near a golf course in Japan [1.2.5, 1.3.5]. This bacterium was named Streptomyces avermitilis (later reclassified as Streptomyces avermectinius) [1.3.4]. Remarkably, despite decades of searching, this Japanese soil sample remains the only source of S. avermitilis ever found [1.2.5]. Professor Ōmura cultured thousands of bacterial strains, screening them for medicinal potential and sending them to his research partner in the United States [1.2.5, 1.3.2].
From Discovery to Drug: A Nobel Prize-Winning Collaboration
Dr. Ōmura's collaborator was William C. Campbell, a researcher at Merck Research Labs [1.2.5]. Campbell tested the bacterial cultures provided by Ōmura for activity against parasitic worms that affect animals [1.2.5]. One culture, derived from S. avermitilis, was found to be exceptionally effective [1.2.5]. The active component produced by the bacterium was named avermectin [1.2.2, 1.3.3]. The discovery and development of this compound were so impactful on global health that Drs. Ōmura and Campbell were jointly awarded the 2015 Nobel Prize in Physiology or Medicine [1.3.1, 1.9.4].
Avermectin vs. Ivermectin: A Crucial Distinction
It is critical to understand that the bacterium Streptomyces avermitilis produces avermectin, not ivermectin directly [1.5.4]. Ivermectin is a semi-synthetic derivative of avermectin [1.2.4]. After isolating avermectin, researchers at Merck, including Campbell, found they could improve its activity and safety profile through a simple chemical modification [1.2.2]. By adding two hydrogen atoms (a process called hydrogenation) to the avermectin molecule, they created the more potent and less toxic ivermectin [1.2.2, 1.5.1]. Ivermectin is technically a mixture of two such modified compounds, comprising approximately 90% 22,23-dihydroavermectin B1a and 10% 22,23-dihydroavermectin B1b [1.11.3]. This semi-synthetic process—starting with a natural molecule and chemically refining it—is a common practice in pharmacology, also used for drugs like aspirin [1.2.2].
The Manufacturing Process
The commercial production of ivermectin is a multi-step process that begins with large-scale bacterial fermentation [1.11.1, 1.11.2].
- Fermentation: Streptomyces avermitilis is grown in large fermentation tanks to produce avermectin [1.11.1].
- Extraction: The avermectin compounds are extracted from the fermentation broth and purified [1.11.2].
- Hydrogenation: The purified avermectin undergoes a chemical reaction in hydrogenation reactors to convert it into ivermectin [1.11.1].
- Purification and Crystallization: The resulting ivermectin is further purified, crystallized, dried, and prepared into final pharmaceutical formulations [1.11.1].
Comparison of Avermectin-Family Drugs
The discovery of avermectin paved the way for several related and powerful antiparasitic drugs used in both veterinary and human medicine. Here is a comparison of some key members of this family:
| Drug | Derivative of | Primary Use | Key Characteristics |
|---|---|---|---|
| Ivermectin | Avermectin | Human (River Blindness, filariasis) & Veterinary (broad-spectrum) [1.7.1, 1.7.2] | A disaccharide, semi-synthetic via hydrogenation. The most well-known of the group with wide applications [1.5.4]. |
| Doramectin | Avermectin | Primarily Veterinary [1.10.1] | A disaccharide produced by a mutant strain of S. avermitilis. Very similar in potency to ivermectin against certain parasites [1.10.1, 1.10.3]. |
| Selamectin | Doramectin | Primarily Veterinary (e.g., fleas, heartworm in pets) [1.10.4] | A monosaccharide and oxime derivative. This structural difference makes it less potent against certain internal worms compared to ivermectin but effective topically [1.10.1, 1.10.2]. |
A Legacy of Global Health
The discovery of ivermectin has had an immeasurable impact on human and animal health. In 1987, Merck committed to donating the human formulation of the drug, Mectizan®, for the treatment of onchocerciasis (River Blindness) for as long as needed [1.8.1]. This Mectizan® Donation Program (MDP), later expanded to include lymphatic filariasis (elephantiasis), has provided over 4.4 billion treatments and reaches over 300 million people annually [1.8.1]. This effort has led to the elimination of river blindness in four Latin American countries and has drastically reduced the burden of these diseases in Africa [1.8.1, 1.9.1]. It stands as one of the most successful and longest-running public-private health partnerships in history [1.8.2].
Merck's Mectizan® Donation Program
Conclusion
The natural source of ivermectin is not a plant or herb, but a unique bacterium, Streptomyces avermitilis, originally found in a Japanese soil sample [1.2.5]. The bacterium naturally produces a compound called avermectin. Through chemical modification, scientists created the more effective semi-synthetic drug, ivermectin [1.2.2]. This Nobel Prize-winning discovery has revolutionized the treatment of devastating parasitic diseases, saving millions from blindness and debilitating illness through a combination of brilliant science and unprecedented philanthropy [1.9.4, 1.8.1].
