A Microorganism Found Near Omura’s Home

The Omura Laboratory has been discovering microorganisms that are still unknown to the world and has been steadily researching to find new chemical substances made by such microorganisms. On a sunny day in the autumn of 1975, Omura saw a rotten pumpkin in a vacant lot near his home in Seta, Setagaya-ku, Tokyo. He took a look inside the vegetable

“Hmm…there is a rhizopus nigricans (a type of mold) growing. There must be some good microbes living there.“ Omura took out a small plastic bag which he always carries in his work bag and scooped up the moldy portions from the pumpkin. He took it to his lab and asked his colleague in charge of separating fungus to investigate into it. Then, it turned out that over 10 types of microorganisms coexisted in this mold.

Then they purely cultured each microorganism and studied whether they would produce chemical substances with varied properties. And they found out that microorganisms belonging to actinomycetes were creating new substances that prevent infection from viruses. They immediately investigated the structure of this chemical substance and tried to find out how this chemical substance prevents virus from affecting animals.

Whenever Omura went out, it was customary for him to bring back some soil from his destination. One day, he picked up a morsel of soil near a golf course in Ito-shi, Shizuoka prefecture, where he played golf. He scooped up the soil and brought it back to the lab in his plastic bag. As usual, Omura was working with his staff, separating the microorganisms in the soil, culturing some and checking to see whether they were producing new chemicals.

When they found that a certain microorganism was making a new useful chemical substance, they would place that microorganism in a test tube and attach a serial number. That number would become the name of the microorganism. Yoko Takahashi, who got her doctoral degree after graduating from high school, found and classified microorganisms which were particularly producing various substances, among all others. She thought that the microorganisms in the soil brought back by Omura near the golf course might be producing some good chemicals. Omura looked at the data analyzed by Takahashi and said, “This microorganism may be making some useful chemicals. Let’s send it to Merck and let them investigate more.” A research staff attached a reference number “OS-4870" to the test tube and sent it to Merck. The initials “OS” at the beginning of the reference number stood for Omura Satoshi. As expected, certain chemical substances made by this microorganism led to a major discovery that would later change the world.

Experiment at Merck

The culture fluid OS-4870 from Omura Laboratory was going to be studied further at Merck’s team which developed medicine for animals. This team was headed by Dr. William Campbell.

Looking at research data sent from Omura’s lab, it certainly was an unknown microorganism. Chemical substances made from this microorganism are also unknown and the Merck team felt that it was necessary to investigate jointly with Omura’s lab in the future. Since Dr. Campbell and his colleagues were investigating the usefulness of chemicals through various animal experiments, they decided to examine OS-4870 in mouse experiments.

Dr. Campbell’s team fed the culture fluid OS-4870 to a mouse which was intentionally infested with parasites. When the mouse took OS-4870, the parasites started to decrease. Something in OS-4870 could be killing the parasite. The research team repeated the same experiment many times. The parasites were definitely decreasing. These results were immediately reported back to Omura.

In response to this, Omura decided to first examine what type of microorganism the culture fluid contained.

OS-4870 Gets Rid of Cattle Parasites and Mites

Although OS-4870 was effective with mice that artificially harbored parasites, Merck's research staff thought that other animals could also be cured. Many parasites inhabit the stomach and intestines of grazed cattle. Sometimes more than 50,000 parasites are found. Since the experiment results from the mouse was positive, Merck staff tried it on a cow by having the cow drink the OS-4870 fluid. Again, the culture fluid was killing parasites. But there was more.

Mites that extract nutrients from cattle skin would spread quickly to weaken the cow gradually. Sometimes they could even die from mites. However, cattle that have been administered with OS-4870 would start to lose mites. Merck was astonished at this result. The culture fluid did indeed contain chemical substances that can kill parasites and mites. Consequently, researchers tried to discover this substance and finally succeeded in specifying it. The team named the chemical “avermectin.”

Similarly, staff at Omura’s lab were also studying the structure of avermectin sent back from Merck and investigated the class of actinomycetes which were producing this chemical substance. And Takahashi precisely classified this microorganism and named it Streptomyces avermectinius.

Experimental Results

For the experiment, Merck selected 24 cattle at random. At random means that they are not chosen with any purpose in mind, but are chosen by chance. 24 cattle were divided into Group A and Group B, with 12 cattle in each group. 12 cattle in Group A drank 200 micrograms (1/5000 gram) of avermectin only once. Cows in group B did not take the avermectin fluid at all.

Results showed that parasites were completely gone for the 12 cattle in Group A which swallowed avermectin. Parasites remained intact in the 12 cattle of Group B which did not take avermectin. In average, 99.9 % of parasites perished in cows that took avermectin. Omura and Campbell were surprised of its efficacy. Just by administering it once, it demonstrated great improvement. Immediately, Merck decided to file a patent for avermectin so they can develop a medicine for animals.

If you keep a dog as your companion, you may be familiar with filariasis. In the past, many dogs died from filariasis. In filariasis, a filaria parasite inhabits the heart of the dog and endangers its life. Avermectin proved to work for filaria too. This parasite could also be exterminated with just one dose. It became possible for dogs to live longer because they did not have to suffer from filariasis anymore.

Furthermore, it was found that the effect of avermectin was not limited to filariasis, but was also proven effective for arthropods like leaf mites and spider mites. It was found that avermectin also exerted effect in exterminating mites that specifically cause damage to plants, and it came to be widely used in agriculture and horticulture. Avermectin became Merck’s prime hit product. Its sales which started in 1981 had shot up rapidly and from 1983, it became a top runner in the sales of animal medicine for 20 consecutive years.

As advisor to Sumida Tech’s
Omura (left) and Campbell Who Partnered to Find Avermectin, the Discovery of the Century
As advisor to Sumida Tech’s
Yoko Takahashi (right) Who Precisely Categorized and Presented the Avermectin-Forming Bacteria
https://www.kitasato-u.ac.jp/lisci/english/kitasato-LIS/ILS-Lab24en.html
As advisor to Sumida Tech’s
Omura Explains by Showing the 3D Model of Avermectin