During and after World War I, the need for infectious disease control was higher than ever. Disinfectants that appeared in the 19th century had improved considerably, but were powerless against bacteria that had already grown in the body.

In the early 20th century, salvarsan, which is effective against the pathogen of syphilis, was developed by Ehrlich and Hata and others, paving the way for chemotherapy for infectious diseases. Inspired by this, many researchers have begun to search for compounds that are effective against various bacteria. But those attempts had little fruit in him. Some were effective in vitro but not in vivo. Some killed pathogens efficiently, but also had a strong negative effect on laboratory animals.

Ehrlich himself worked energetically to create a drug that would follow salvarsan. But all the compounds he tested by the time he died at the age of 61 had failed. The only successful example, salvarsan, was also severely criticized for its strong side effects. The stress he received here may have shortened his life.

In the mid-1920s, pessimism was widespread in how chemicals were used to treat infectious diseases. Some remedies have emerged, but none have been adequately effective against tropical protozoan infections. Chemotherapy remains powerless against the bacterial infections that have plagued humanity, such as cholera, plague, and dysentery. Many people withdrew from research because they gave up on the fact that bacteria could not be defeated with the weapon of chemical substances.

​

There were those who dared to challenge this seemingly hopeless territory and invest huge amounts of money and personnel. It was Hörlein, head of the pharmaceutical research division at I.G. Falben, a giant chemical contour in Germany.

Hörlein needed a good pathologist to create a truly effective drug. It was young researcher Gerhard Domagk who read the treatises in the relevant fields and made a white arrow. At a local university, suffering from a lack of research funding, he jumps at Hörlein's invitation. Thus, in 1927, Gerhard Domagk's talent was combined with the world's best research environment.

Gerhard Domagk was a medic in the Ukrainian battlefield when he was young and witnessed the dire situation of gas gangrene. He was determined to fight this bacterial infection, which claimed the lives and limbs of many of his companions, for a lifetime.

Gerhard Domagk set up his research system in a building built for him. Should be tested

A team for synthesizing compounds, a team for investigating the effects on various pathogens, a team for investigating what kind of reaction occurred in the body of laboratory animals, etc. were formed, and a system that works in an orderly manner was constructed. If Ehrlich and Qin created the prototype for drug discovery, then Gerhard Domagk was the first to put in place a modern drug discovery system.

They were very German and worked hard. Gerhard Domagk himself conducted the experiment on "histopathological examination", in which the organs of experimental animals were sliced ​​thinly and stained to confirm the site of infection, without leaving it to others. However, even four years after the start of the project, no light was visible.

The veins were finally found in the summer of 1931. Dye compounds that have supported the prosperity of the German chemical industry include a group of compounds called azo compounds. These were compounds in which two nitrogen atoms were bonded so that two benzene rings were sandwiched between them. While trying various parts bonded to this benzene ring, I found one that was more effective than ever. Some of them not only extended the lives of infected laboratory animals, but even completely restored them.

But the joy of the team didn't last long. The test results are not stable. Even a slight change in the fabrication would change the effect completely, and even if the same product was made and retested, the original results were often not reproduced. We have already tested about 3000 compounds, and even if we try to synthesize a new compound that breaks through the situation, new ideas are already exhausted.

When you run out of ideas, bringing in ideas from other disciplines often leads to good results. At this time, the new proposal was made by Hörlein himself, the head of the pharmaceutical research division. When he searched for a dye to dye wool, he experienced that when he attached an atomic group containing a sulfur atom called a namide group to the benzene ring, it became a dye that was hard to remove. His idea was that a compound that easily binds to wool might also easily bind to bacteria.

In the fall of 1932, a sulfonamide group was attached to an azo compound and his compound was synthesized. The results of administering the synthesized wine red compound to animals were truly amazing. When the compound was given orally or by injection to a streptococcal-infected mouse, almost everything was completely recovered.

Unbelievable, the result was too good, and the team retested many times, but Maus was still sick. The only side effect was that the skin became reddish for a while after administration. It was the moment when humans first acquired an effective weapon against bacterial infections that had been plagued for a long time. Since this compound contains sulfur, it will be called a sulfa agent.

As it turned out later, the azo group, which was initially thought to be the main body of the action of sulfa drugs, was not directly related to the action of killing bacteria. The sulfonamide group, which was introduced to facilitate binding to bacteria, was the key to its antibacterial activity. It was found that even a simple compound (pure sulfa) that does not have an azo group and has only a sulfonamide moiety has a high antibacterial effect, and currently only this compound is used.