In 1919, a French doctor’s accidental discovery opened the curtain on viral therapy. However, with the rise of antibiotics, this medical method of using bacteriophages to fight drug-resistant bacterial infections has rapidly declined after a period of prosperity. Nowadays, as the problem of antibiotic resistance becomes more and more serious, more and more funds and personnel are returning to the research of viral therapy This “ancient” therapy has finally ushered in the hope of “resurrecting the dead”.

This article is from WeChat official account:Global Science (ID: huanqiukexue), Luo Dinghao, original title: “Injecting a virus into the human body: This therapy, which was abandoned nearly a hundred years ago, has finally come back to life”, head picture from: Gregory & Marshall/Wellcome Collection

When the 47-year-old Frenchman Esteban Diaz(Esteban Diaz, pseudonym) set out for Georgia, he clearly realized This violated the doctor’s advice, but he couldn’t hold it anymore.

Diya who suffers from cystic fibrosis(cystic fibrosis) is very susceptible to bacterial infection, so he has been using it under the guidance of a doctor since he was a child Antibiotics, but this time, he was infected with Pseudomonas aeruginosa (Pseudomonas aeruginosa), this “super bacteria” wreaked havoc in his lungs . To make matters worse, all available antibiotics have no effect. The only way out (at least in the eyes of Dia’s doctors) is lung transplantation.

And Dia is not thisWhat do you think: Some Eastern European countries, including Georgia, can provide a “viral therapy (phage therapy, also known as ” Bacteriophage therapy”) is a medical method that sends phage (bacteriophage) into the human body to treat bacterial infections. After receiving the viral therapy, Dia claimed that he recovered within a few days, and the long-term exhaustion, constant coughing and shortness of breath that lasted for decades have all disappeared.

As more and more bacterial infections become extremely difficult to cure, the World Health Organization (WHO) will antibiotic resistance (antibiotic resistance) is listed as a major threat to global health, food safety and development. By 2050, there will be 3000 Ten thousand people are affected by it. For diseases such as pneumonia, tuberculosis, salmonella infection, “professional” antibacterial antibiotics(such as penicillin, tetracycline and cephalosporin antibiotics, etc.) It was supposed to be the first-line drug, but now it is helpless against many pathogenic bacteria. Many European and American countries have therefore turned their attention to the “frontier” approach, that is, viral therapy. Since the beginning of the 21st century, the European and American world has begun to attack the virus therapy program and safety, and has carried out clinical trials in recent years. At present, many virus therapies have entered phase III trials, and clinical use may be coming soon.

Perhaps few people would have thought that this seemingly “frontier” therapy became popular in Eastern Europe in the 1930s. The recent “resurrection” of this ancient therapy is perhaps the greatest and only hope for millions of suffering patients.

Bacteriophages

Viruses are ubiquitous and diverse in appearance. I am afraid that none of the pupils who saw the electron microscope (electron microscope) image of the virus for the first timeThe method dispels the thought of “This is too subtle!” in my mind. It is estimated that among the viruses covering the world, the number of phages alone has reached at least 1031. Almost every biology textbook has at least one such illustration. The picture shows the appearance of the phage under the electron microscope: several “legs” spread out on the tail of the phage, the tail and the head wrapped in DNA Connected by a “pole”.

Left: Electron microscope image of a single phage. Image source: Miller et al., Microbiol. Mol. Biol. Rev.

Right: Electron microscope images of many phages attached to bacterial cell walls. (Image source: Graham Beards shared through CC BY-SA 3.0 agreement)

As the name of the phage describes, the phage “feeds on bacteria”. There are tens of millions of bacteria in the world. Phages that have co-evolved with bacteria have naturally evolved into tens of thousands of different species, each of which specifically targets one type of bacteria. For example, the well-known T2 phage uses Escherichia coli as its host to infect and kill Escherichia coli. After “landing” in an E. coli cell, the T2 phage can inject its genetic material into the bacterial cell. Before long, the bacteria will become a huge “virus factory”, producing and assembling the components of bacteriophages at an extremely high speed. Soon, after producing enough “cloned” viruses, the phages will order the lysis period to begin, and the bacteria will “explode” and release a large number of phages into the external environment.

For bacteria, this is not good news. In fact, the first time humans discovered the existence of bacteriophages originated from the blank dots in the laboratory bacterial petri dishes-in these dots, the bacteria seemed to disappear as a mystery, as if there was some unknown force. Stop their growth. In 1916, in the Pasteur Institute (Pasteur Institute) Felix Dihely who works(Felix d’Herelle) was appointed to analyze the causes of dysentery among French soldiers. He found that these blank dots were more likely to appear in petri dishes containing stool samples of certain French soldiers, and these French soldiers usually showed rapid improvement in dysentery symptoms. Di Hailai immediately realized that whatever the substance in these dots, it must have a relieving effect on dysentery. Three years after the discovery of this phenomenon, Di Hai Lai successfully extracted the substance in the blank dots of the petri dish, and planned to provide this substance as an antidote to dysentery to patients suffering from hemorrhagic dysentery. In order to persuade patients and doctors, he also took the lead in drinking a “drink” mixed with this substance. “It’s not delicious, but at least it’s not too bad,” Dihailey wrote in the record.

In one of the Petri dishes in Dihailai’s laboratory in the 1930s, the blank dots formed by phages killing bacteria are clearly visible. (Image source: Institut Pasteur/Felix Dihaile Archives)

After drinking the “drink” provided by Dihailai, the patient’s bleeding dysentery quickly eased. This treatment more than 100 years ago was the first time that a virus was used to treat bacterial infections. Viral therapy research was unacceptable and quickly entered its heyday in the 1920s. In 1925, the Royal Netherlands Academy of Arts and Sciences (KNAW) awarded Dihaily the Lewenhoek Medal once every 10 years. In 1934, Di Haile entered the Soviet Union at the invitation of Stalin and arrived in Tbilisi, Georgia.(Tbilisi), together with his old acquaintance George Eliava(George Eliava), Began to work at the Tbilisi Institute. For a time, the Soviet Union occupied a leading position in the research of viral therapy.

The good times will not last long, and the offensive of viral therapy in the medical market will soon disappear. In 1928, scientists discovered penicillin (also known as penicillin). In 1930, the first clinical application of penicillin was successful. Since the 1940s, antibiotics such as penicillin have occupied a large area of ​​the medical market in European and American countries, and research on viral therapy has gradually declined.

Then, as the Cold War began, viral therapy disappeared in most European and American countries.

return to life

March 2016, Tom Patterson (Tom Patterson) lying in La Jolla, California(La Jolla) a bed in an intensive care unit. Patterson is a professor of psychiatry, and a severe bacterial infection robbed him of most of his consciousness and breathing ability. “He is like a living skeleton,” Patterson’s wife said. He was dying, and the hospital could do nothing: They tried all the antibiotics that could be used, but they had no effect at all. In desperation, Patterson’s doctor decided to give it a go and sent an urgent message to the U.S. Navy. The message is clear: in the absence of antibiotics, the hospital wants to try the virus therapy that the Navy is developing.

After receiving the request for help, Lieutenant Commander and Biologist Syron Hamilton (Theron Hamilton) hesitated for a while. In the end, he chose to help Patterson. On March 17, La Jolla ushered in the US Navy’s phage. Soon, the phage entered Patterson’s vein. Two days later, after a coma that lasted for several weeks, Patterson woke up.

Like Estaibang Dia, Patterson is also one of tens of millions of people affected by bacterial resistance.

Phage produced by the George Yeliava Institute. (Image source: George Yeliava Institute)

However, the “new” interest in the international medical community for viral therapy shows that in the fight against drug-resistant bacteria, a ray of light is shining slightly. Hundreds of millions of tiny phages once brought Patterson back to life, and now, the influx of hundreds of millions of funds and researchers may also bring viral therapy back to life.

This article is from WeChat official account:Global Science (ID: huanqiukexue)< span class="text-remarks">, Luo Dinghao