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Isabelle Holdaway, 15, was short of options. After receiving a lung transplant made necessary by her cystic fibrosis, she contracted an infection that did not respond to antibiotics. His liver was failing. His skin was covered with lesions. His chances of survival were less than 1%.
But today, a few months later, she is much better – thanks, apparently, to a virus taken from the bottom of a rotten eggplant in a soil teeming with worms.
Holdaway, who lives in London, has been treated with an experimental "phage therapy" developed by her local doctors and researchers at the University of Pittsburgh. Phage – viruses that infect and destroy specific bacteria – are often found in very dirty places. Ditches. Ponds. Waste.
The idea of intentionally dosing your body with a virus found in such conditions could cause a thrill of disgust. But as many infections become resistant to traditional medications because of our chronic overuse of antibiotics, more patients are turning to phage treatment as a last resort.
And some scientists are racing to meet the demand. They scour the world for new viruses, then store them in freezers, assembling vast libraries of phages. Pittsburgh's contains over 10,000 different viruses, which can be used to target different strains of bacteria.
Holdaway was treated with a cocktail of three phages. One comes from the aforementioned eggplant, found in South Africa in 2010. The other two, found in the United States, have been genetically engineered to become more effective killers of the Holdaway bacteria. Her case was the first time that a patient was treated with genetically modified phages.
She still follows this treatment twice a day, but her health has already improved considerably. The infection has been controlled. His liver is restored. The lesions have mostly disappeared.
It's a pretty amazing story, but it's important to note that it's not a complete clinical trial. Scientists can not say for sure that phage therapy saved Holdaway's life. However, Benjamin Chan, an associate researcher at Yale University who did not participate in the study of his case, told me that there was "a very, very good chance" that the phages would be responsible for it. . "You have seen an improvement in correlation with the phage administration," he said.
Holdaway is one of many patients who have had positive results after phage therapy. This treatment gives a bit of hope at a time when standard antibiotics are starting to fail miserably. Already, 700,000 people worldwide are dying each year from drug-resistant diseases, including 230,000 multidrug-resistant TB deaths. And the problem only worsens.
How phage therapy was found, lost and found
This therapy may seem odd, but it is not new, it goes back a century. Phage have often been used to treat infections during the first decades of the 20th century, and in some parts of Eastern Europe and Russia this is still the case.
But in the West, phages were mostly abandoned with the arrival of antibiotics. The new class of drugs was easier to use and more versatile: an antibiotic can be used to treat many different infections, while a phage is much more specific: it can infect only a particular strand of an a particular kind of bacteria.
Another advantage of antibiotics is that instead of looking for them in the middle of pond scum and wastewater, you can make them in the laboratory. It was a clean and practical solution that saved millions of lives.
The problem is that, almost as soon as a new antibiotic is introduced, the bacteria it targets begin to evolve in response, developing resistance to the drug. And for decades, doctors, farmers and others have pushed the resistance by distributing an overabundance of antibiotics.
The result? Not only infections such as tuberculosis, but also common problems such as STDs and urinary tract infections become resistant to treatment. According to a new UN report, if we do not make a radical change now, drug-resistant diseases could kill 10 million people a year by 2050. It's more people than people who are dying now cancer.
It is an impending emergency that has so far gone almost unnoticed by the American public. Large pharmaceutical companies, after determining that there is not much money to be earned in the research and development of new antibiotics, also tend to ignore it. But for patients already suffering from drug-resistant diseases, the urgency is there and now. They are desperate for treatment, even if it has not been tested.
Enter the phage therapy.
How does therapy work
A typical phage looks like a lunar lander. When he comes in contact with a bacteria, he uses his "feet" to hang on to it. He injects his own DNA into the host, then begins to reproduce, making so many copies of himself that he eventually burst the bacteria.
The operation of phages has several advantages. Because a phage is so specific to its host, scientists can deploy phages that will capture only the bacteria that they want to eradicate – unlike broad-spectrum antibiotics, which often kill the good bacteria in your intestine and the bad ones. Better yet, the deployment of phages can cause the bacteria to evolve in response, which sometimes involves moving from antibiotic resistance to antibiotic sensitivity.
This is a good result because it means that patients have more treatment options: after following a cycle of phage therapy, they can supplement it with a series of antibiotics, which can now actually suit them – as seems to be the case for one of Chan's patients. with cystic fibrosis.
Phage is thought to be the most abundant form of life on Earth. At any time, it is estimated ten trillion trillion from among them drifting around. So, how do scientists find the right ones?
"It's an enlightened idea," said Chan, who has researched phages across North America, South America, sub-Saharan Africa, and Asia.
Since phages are highly dependent on their hosts, which are certain strains of bacteria, you have to go to places where you can find the bacteria you want to kill. For example, if you want to find phages that kill the bacteria that cause cholera, you have to go to a country that still has cholera outbreaks, maybe a country that does not have a good treatment system. the water. You would take a sample of water, bring it to your laboratory and genetically sequence the phages it contains. You would identify if and how a phage attaches to the bacteria responsible for cholera. Then you store it in flasks in your freezer so that it is there, waiting for the day a sick patient calls and asks for help.
Chan's work around the world is not glamorous. "We often go to wastewater treatment plants and we just pick up the wastewater," he said. "A lot of the phages are in wastewater because that's where there are many bacteria associated with human activities."
But he is encouraged to see the dirty work pay off. In the last three years, he said, he has noticed a growing enthusiasm for phage therapy. At Yale New Haven Hospital, he and his colleagues have treated 16 patients with phage therapy since last week. "This number is fast becoming crazy," he said, adding that he was receiving new treatment requests every day. As his list of potential patients lengthens, he hopes to start a clinical trial by the end of the year.
All patients who seek phage therapy do not end up getting it. As it has not been tested, it can only be legally administered on a humanitarian basis – that is, only when all standard treatments have failed. For each case, scientists must demonstrate to the FDA that other treatments have not improved the patient's health and explain how the phages will help to get the job done. In case of emergency, FDA approval can be obtained in a few hours.
Chan thinks that once the clinical trials are complete, phage therapy will quickly become more popular. He acknowledged the risk of getting injected with a virus taken from wastewater, but said that when someone has a really terrible infection, he quickly overcomes this psychological hurdle. "In the cases we are treating, people have been suffering from these infections for years and the situation is getting worse," he said. "These people are like, 'Dude, just fix it."
But the phages will not solve the problem of each patient. Some researchers noted that they were very specific to the host and that therapy was therefore limited to broad-spectrum antibiotics. Finding a phage that can work on a specific strain of specific bacteria may take some time, sometimes too much. The same London doctors who cared for Holdaway also tried to cure another girl with cystic fibrosis, who was suffering from a different strain, but she had died by the time the right phage had been found.
Another hurdle will be for pharmaceutical companies to invest in research and development. But Chan added that he was already receiving requests for information from companies in the Big Pharma group, some of which were working "actively and aggressively in the phage space", including corporations. like Johnson & Johnson and Merck.
Depending on how phage therapy is regulated, this could increase or decrease financial incentives for companies to invest in phage therapy. At the moment, there is no general regulation, but only ad hoc FDA approvals or rejections for individual patients. This therapy is so new in the West that it's hard to say what role it will play. But as the crisis of antibiotic resistance worsens, it is clear that there is an appetite for alternative treatments like this one.
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