1. How Venom Is Turned into Medicine: The Basic Process
The general method is straightforward. Venom from a snake (or venom with its toxicity removed) is injected into an animal, such as a horse, many times in small amounts.[1] As the animal’s body reacts, it produces antibodies against that specific venom. Once enough antibodies have formed, blood is taken from the animal. The antibodies (immunoglobulins) are then extracted, purified, and put into bottles to become medicine.[1]
The World Health Organization (WHO) also explains that antivenoms are made by repeatedly injecting small amounts of venom to immunize an animal, then purifying immunoglobulins from its plasma.[2] The goal is not to make the horse sick. Instead, giving small doses allows the body to build up a defense against that specific poison. Specific numbers for injection amounts or frequencies used in Japan could not be confirmed from public materials.
2. Kitasato and Behring’s 1890 Paper on Serum Therapy
The idea behind this medicine goes back to a paper published on December 4, 1890, by Kitasato Shibasaburo and Emil von Behring.[3] The title was "On the Acquisition of Immunity in Diphtheria and Tetanus in Animals." This work is considered the starting point of serum therapy, which uses immunity found inside an animal’s body to treat diseases in humans.[3]
Emil von Behring received the first Nobel Prize in Physiology or Medicine for this work. Kitasato did not receive the prize. There are various explanations for why this happened, but those details are outside the scope of this article.
3. Applying Serum Therapy to Snake Venom in France in 1894
Researchers in France announced their application of serum therapy to snake venom.[4] On February 10, 1894, two groups—Phisalix and Bertrand, and Calmette—announced their research results on antivenom serum almost at the same time.[4]
Calmette worked at the Pasteur Institute. He was moved by the high number of people dying from snakebites in India and began producing antivenom serum in Lille.[4] A letter from 1891 written by Calmette mentioned a figure of 21,000 deaths per year as official British government statistics. However, this was a number written by Calmette himself at that time, not modern statistical data.[4]
4. Why Horses Are Chosen to Make Antivenom
By 1895, Calmette had produced more cobra antivenom using donkeys, but in that same year, horse serum was successfully used to treat human bite wounds for the first time.[5]
A review article lists one reason for choosing horses: they produce a larger amount of serum from a single blood draw compared to other animals that are easier to handle and raise.[5] In Japan, the choice is explained by two factors: the long history of using horse-derived products in humans, and caution regarding zoonotic diseases (infections that can pass from animals to humans).[1] All antivenom preparations made in Japan are derived from horses.[1]
5. Making Horse Antibodies Smaller with Pepsin Treatment
Horse antibodies are foreign substances to the human body. If they stay inside a person for too long, the human body may start making antibodies against the horse antibodies.[6] It is said that side effects are more likely to occur if the medicine is used again later.[6]
To solve this, scientists developed a way to fragment the antibodies. When treated with the digestive enzyme pepsin, the antibody (IgG) separates into the part that binds to the venom (F(ab')2) and another part called the Fc region.[6] Molecular weight is a number representing the size of a molecule. The molecular weight of IgG is about 150,000, while the venom-binding part is about 110,000.[6] The remaining part after treatment is smaller than the original antibody. This modification is explained as a way to reduce side effects caused by the animal origin of the medicine.[6]
In the description for Mamushi (pit viper) antivenom, about 80% of the components are F(ab')2, 10% are IgG, and 10% are Fc fragments. The Fc fragments leave the body quickly.[6] Note that this description applies to Mamushi antivenom and may not apply exactly to other antivenoms.
6. Why Each Snake Type Needs Its Own Antivenom
Antivenoms are made for specific types of venom. For example, Mamushi antivenom cannot treat a bite from a Yamakagashi (red-banded snake), and the reverse is also true.[6] This is because the components of venom differ by snake species, and the antibodies bind to specific targets unique to each venom.[6]
Mamushi antivenom was prototyped at the Institute for Infectious Diseases, where Kitasato served as director, using Mamushi venom from Amami Oshima. It was completed in 1904. Today, Mamushi venom from Amami Oshima and Okinawa Island is used.[6]
Dried Mamushi antivenom is made by purifying serum from horses immunized with Mamushi venom or toxoid (a modified toxin), then freeze-drying it. The manufacturer is KM Biologics.[7]
Yamakagashi antivenom was prototyped by extracting venom from the neck glands (Duvernoy's glands) of about 500 healthy Yamakagashi snakes. The toxicity was removed using formalin, and then two horses were injected multiple times.[8] This was only a prototype; it is not currently supplied as a standard medicine. In the past, researchers at the Japan Snake Society also prototyped versions using rabbits and goats.[8]
KM Biologics (formerly the Chemicals and Serum Research Institute in Kumamoto) is listed as a facility that manufactures antivenoms and antisera in Japan.[9]
7. How to Learn More by Drawing the Antivenom Process
Try drawing the flow of this process on paper: "Venom → Horse’s body → Antibodies → Taken from blood → Reaches a person." Connect these steps with arrows.[10] Then, compare your diagram with books or pages from public institutions to see what might be missing.
This article is not medical advice. If you are worried about snakes or injuries, please consult your school or family, or read official guides from medical institutions.[10]