The Origin Story: The Discovery of Streptomyces avermitilis
Ivermectin is not a naturally occurring compound, but is derived from a natural source through a semi-synthetic process. The remarkable story begins with a small soil sample collected in 1973 by Japanese microbiologist Satoshi Ōmura from a golf course near Tokyo. After culturing thousands of microorganisms, he identified a new species of soil-dwelling bacteria, which he named Streptomyces avermitilis.
Recognizing the potential for new medicinal compounds, Ōmura sent cultures to Merck Research Laboratories in New Jersey. A team led by parasitologist William Campbell tested these cultures against parasitic worms in mice, leading to the identification of a family of compounds with potent antiparasitic properties. These were named avermectins. This collaborative discovery earned both scientists a Nobel Prize in 2015 for their groundbreaking work.
From Avermectin to Ivermectin: A Chemical Modification
The avermectins produced by the bacterium were powerful antiparasitic agents, but researchers at Merck sought to create an even more effective and safer version. Their work led to a simple yet impactful chemical modification. By hydrogenating the double bond at the C22–C23 position on the avermectin B1 molecule, they created ivermectin. This slight chemical alteration resulted in a compound with improved characteristics for therapeutic use. The final product, ivermectin, is therefore described as a semisynthetic macrocyclic lactone.
The Role of Fermentation in Production
The large-scale production of avermectins relies on the natural capabilities of Streptomyces avermitilis in a controlled environment. The process typically involves several key steps:
- Culturing the Bacteria: The S. avermitilis strain is grown in large bioreactors under carefully controlled conditions. The medium contains specific nutrients, such as soluble starch and yeast extract, optimized for the bacteria's growth and avermectin production.
- Fermentation: The bacteria produce the avermectins, which are released into the fermentation broth. The duration and conditions of the fermentation process are fine-tuned to maximize yield.
- Extraction and Purification: After fermentation, the avermectins are extracted from the bacterial biomass. This is followed by a rigorous purification process to isolate the active compounds, primarily avermectin B1a and B1b.
- Chemical Modification: The purified avermectin B1 is then chemically hydrogenated to produce ivermectin.
Avermectin vs. Ivermectin: Key Differences
It is crucial to differentiate between the naturally produced avermectin and the final, semisynthetic ivermectin. The table below highlights their main differences:
| Feature | Avermectin (Natural Precursor) | Ivermectin (Semisynthetic Drug) |
|---|---|---|
| Origin | Natural fermentation product of the soil bacterium Streptomyces avermitilis. | Produced by chemically modifying the natural avermectin B1 molecule. |
| Chemical Structure | Contains a double bond at the C22–C23 position within its lactone ring structure. | This double bond is selectively reduced (hydrogenated), resulting in a single bond. |
| Composition | Consists of a mixture of eight related compounds, with B1a and B1b being the most potent. | A mixture primarily consisting of 22,23-dihydroavermectin B1a and B1b. |
| Biological Activity | Potent antiparasitic effects against a variety of worms and insects. | Enhanced potency and a better safety profile for therapeutic applications. |
| Primary Use | Precursor for ivermectin and also used as an agricultural insecticide, known as abamectin. | Widely used in both human and veterinary medicine for parasitic infections. |
The Unprecedented Impact of a Microbial Product
The discovery of avermectins and the development of ivermectin had a revolutionary impact on both animal and human health. It provided the world with a powerful new tool against parasitic diseases that had plagued populations for centuries.
- Veterinary Medicine: Introduced for veterinary use in 1981, ivermectin quickly became a top-selling drug for treating parasites in livestock and companion animals. Its effectiveness against internal and external parasites was unprecedented.
- Human Health: In 1987, ivermectin was approved for human use and soon became a cornerstone of global public health campaigns. It is the essential drug in campaigns to eliminate onchocerciasis (river blindness) and lymphatic filariasis (elephantiasis). Merck's Mectizan Donation Program has been instrumental in providing the drug freely to affected communities.
This success story highlights the critical importance of exploring natural resources, particularly soil microorganisms, for potential new drugs. The Earth's soil is a massive reservoir of biological diversity, and many beneficial compounds, like penicillin and other antibiotics, have been derived from its microbes. The collaborative effort that produced ivermectin from a simple soil sample shows the immense value of natural product drug discovery.
Conclusion: The Semisynthetic Legacy
In conclusion, the answer to "Where is ivermectin found naturally?" is that it is not. Instead, the drug is a product of human innovation, derived from a naturally occurring family of compounds called avermectins. These avermectins are produced by the unique soil bacterium Streptomyces avermitilis, which was discovered in Japan. The subsequent chemical modification to create ivermectin transformed a promising natural product into one of the most significant and impactful drugs in modern history, forever changing the landscape of parasitic disease control for both animals and humans. For further reading on the history and impact of ivermectin, explore the article "Ivermectin, 'Wonder drug' from Japan: the human use perspective" available on the NIH's website.
