In order to cure this disease, he did not hesitate to go to court!

Author's note: In the elementary school Chinese textbooks of our generation, there was an article titled "The Man Who Writes to Himself," which actually tells the story of how Ehrlich found an effective drug to treat syphilis, but the word syphilis does not appear in this text.

I guess that with the level of rural primary school teachers at that time, they probably didn't know what kind of disease the drug studied by Ehrlich was used to treat. It was the mid-1990s when quack doctors posted advertisements for the treatment of syphilis on all telephone poles and toilet walls across the country.

The model of using effective drugs to treat infectious diseases that we are familiar with today was started by a hidden disease that is difficult to talk about. It is difficult to estimate how many lives this treatment model has saved after modern medicine gradually matured. But who would have thought that this treatment model that saved countless lives was triggered by people's concern about a sexually transmitted disease?

While sex fosters love and reproduces life, it also spreads the most disgusting diseases. Among this large category of diseases, the one with the greatest impact in history is syphilis.

How does syphilis come about?

Humanity's attention to syphilis began in the 1490s, but the exact time and specific geographical location of the origin of syphilis are still unclear . Both the American origin theory and the Old World origin theory have their supporters. Historians seem to enjoy this debate and have no intention of coming to a convincing conclusion from this debate.

In an era when there was no cure, syphilis was dangerous, and out of fear of the disease, people from different countries began to use it as an excuse to attack each other and blame the outbreak on specific groups of people.

For example, in the 16th century, the British firmly believed that syphilis came from France, so they called it French pox. The French, on the other hand, firmly believed that the disease came from Naples, Italy, so they called it Neapolitan disease. In Russia, syphilis was called Polish disease. In Poland, the disease was called Turkish disease, and Turkey simply called syphilis Christian disease. When the disease spread to China, the Chinese once called it Guangchuang.

Treatment of early syphilis is confusing

William Osler, a famous medical educator, once said: Syphilis is a great imitator... He who understands syphilis understands medicine. This statement emphasizes the clinical diversity and complexity of syphilis, which can affect all systems of the body at different stages of the disease : primary syphilis can cause chancres on the patient's vulva, secondary syphilis can cause rash, fever and widespread lymphadenopathy, and tertiary syphilis is characterized by progressive destruction of the skin, mucous membranes, bones and internal organs. In the most serious cases, it can affect the cardiovascular system (such as aneurysm formation) and the central nervous system (such as paralytic dementia).

In the era of microbiology pioneered by Pasteur and Koch, pathogenic microorganisms were identified one after another. In 1905, German zoologist Fritz Schaudinn (1871-1906) identified the cause of syphilis - a linear spiral bacterium, which the medical community later named Treponema pallidum. The following year, a method for detecting syphilis appeared.

Treponema pallidum source: Wikipedia

At that time, the treatment options for syphilis were very limited. In the 16th century, Paracelsus (1493-1541) began to use mercury to treat syphilis . Although this method could alleviate some of the symptoms caused by syphilis, the side effects it brought were no less harmful to the human body than the original disease, such as tooth loss, severe indigestion, and even death. It was a treatment that killed eight hundred enemies but hurt one thousand of its own.

Before the advent of modern medicine, many treatments were like this: either completely ineffective or equally beneficial, and the patient's choice seemed to be only between dying from the disease and dying from a doctor . For people of that era, once they encountered a disease, whether to treat it or not was really a dilemma.

Ehrlich discovered

New drug for syphilis

Regarding the treatment of diseases, German doctor Paul Ehrlich (1854-1915) proposed a very tempting idea: is it possible to design a drug that only attacks the pathogens that cause the disease while being safe for the human body?

Ehrlich's messy studio. Source: Frankfurt History Museum

The theoretical basis of this concept is that chemical substances have specific points of action in organisms. If we can find chemical substances that have little affinity with body cells but have affinity with pathogens, we can achieve the goal of killing bacteria without harming the human body.

Why did such an idea come into Ehrlich's mind?

It turned out that in the process of studying tissue staining, he found that the ability of a certain dye to stain a certain tissue is related to the chemical affinity of the dye with a specific tissue , that is, the biological effect of the dye depends on the affinity of the substance with different structures in the tissue. Ehrlich inferred from this that there is a drug that can produce a certain biological effect without producing undesirable adverse reactions? After all, in the laboratory, the number of compounds that can be produced in theory seems infinite.

Starting in 1909, Ehrlich and his assistant, Hanasahiro, tested many compounds and eventually found that dihydroxy-diamino-arsenic benzene, numbered 606, could be used to treat syphilis in rabbits . But Ehrlich knew that many seemingly promising drugs were later abandoned because of unsatisfactory effects or severe side effects. Could 606 be an effective drug for treating syphilis?

As subsequent trials continued, 606 increasingly showed promise in treating syphilis. In order to advance clinical trials, the institute produced a total of 65,000 doses of the drug, which were provided free of charge to trusted doctors for use on syphilis patients.

By 1910, doctors participating in the experiment reported a large number of successful treatment cases. Ehrlich found that 606 was effective for new syphilis, but not so effective for late cases (such as those who had already developed paralysis). After that, Ehrlich named 606 salvarsan (meaning arsenic for treatment) , hoping to end the threat of syphilis to humans .

New drug promotion

Resistance due to side effects

Syphilis had been prevalent in Europe for hundreds of years, leaving the medical community helpless. There was no reason why Salvarsan, which came out of nowhere, would not be warmly welcomed. However, this new drug also encountered considerable resistance during its clinical promotion . Many people criticized Salvarsan for having serious side effects. Some of the comments were so extreme that they were actually slanderous. Many people also believed that Salvarsan could bring huge income to Ehrlich and the pharmaceutical company. As a result, Ehrlich had to write an article to respond to public doubts, explaining how much it cost to research and test new drugs. He also had to go to court to sue to curb serious slander.

Copyright images in the gallery. Reprinting and using them may lead to copyright disputes.

The most outrageous opposition to the use of Salvarsan came from the religious community. Some religious people seemed to believe that Salvarsan could cure syphilis, but they believed that venereal diseases were God's punishment on mortals, so they opposed the use of Salvarsan. (Similar situations also occurred in the process of AIDS research later.)

Facing these opponents, Ehrlich was sober. He did not deliberately ignore or conceal the side effects of Salvarsan to protect his own shortcomings . By 1914, hundreds of thousands of Salvarsan treatments had been carried out around the world, during which 300 cases of serious side effects were reported, with a mortality rate of about 1/1000.

If modern drugs for treating syphilis had a 1/1000 mortality rate, it would certainly be unacceptable, but at that time, choosing Salvarsan to treat syphilis was much better than giving up or choosing mercury treatment.

In order to reduce the side effects of Salvarsan, Ehrlich and his colleagues later produced a less toxic derivative , which was approved for clinical use in 1912 and was named New Salvarsan .

Ehrlich has won numerous honors in his life, such as the Nobel Prize in Physiology or Medicine in 1908 for discovering the role of immune serum and establishing the "side chain" theory. However, many people believe that Ehrlich's most important contribution in his life was actually made after he won the Nobel Prize.

On August 20, 1915, Ehrlich suffered two strokes and never woke up again. At his funeral, his good friend Emil von Behring said in his eulogy: The deceased has become the mentor of the world, he is the teacher of medical science all over the world.

Scientist John Simmons regards Ehrlich as a great figure comparable to Louis Pasteur and Robert Koch. He believes that Pasteur and Koch pioneered the theory of microbiology, while Paul Ehrlich concluded that the essence of disease is chemistry.

If Berling's eulogy may have sounded a little corny to people at that time, then more than a hundred years later, when we stand at today's perspective and look back at the contributions made by this pioneer, we have to agree with Berling's evaluation of him.

Today, the medical community's approach to finding solutions to problems at the molecular level was entirely pioneered by Ehrlich. His idea that drugs could kill pathogenic microorganisms while being harmless to the human body became a reality with the emergence of a series of drugs such as Prontosil and penicillin.

References

[1] https://www.imdb.com/title/tt0032413/?ref_=tttr_tr_tt

Planning and production

Author: Li Qingchen, deputy chief physician of thoracic surgery, Harbin Children's Hospital

Review丨Sun Yifei Director of the Medical Education History Research Office of Hebei Medical University

Planning丨Lin Lin

Editor: Yinuo

Proofread by Xu Lailinlin