The next time you get a stomach bug and antibiotics don’t work, imagine knocking back a vial of clear liquid. This solution contains large amounts of bacteriophages, which are viruses that resemble small rocket ships. These benign microorganisms exclusively attach to and destroy bacteria, and the infection clears up in a few days. Such a future is within reach, writes journalist Lina Zeldovich in a new book Living medicine: How life-saving treatments were nearly lost and why they save us when antibiotics don’t work. The book chronicles the decades-long, sometimes finicky approach to infectious diseases that American science has long ignored in favor of antibiotics.
As microbes develop more sophisticated ways to evade antibiotics, some scientists are returning to bacteriophages, scooping them up from wastewater and testing their pathogen-killing abilities in labs and clinics. I am. Experimental trials are currently underway to test bacteriophage therapy against superbugs such as: Staphylococcus rubervancomycin resistance Enterococcusand stocks of Escherichia coli It is thought to be related to Crohn’s disease. Additionally, some food industry producers are already using Food and Drug Administration-approved phage sprays to remove contamination from their lettuce, sausage, and other supplies. (The treatment has not yet been approved for medical use in U.S. citizens.)
scientific american We spoke with Zeldovich about the differences between bacteriophages and antibiotics, the history of bacteriophage experimentation, and possible future regulation and use in the United States.
About supporting science journalism
If you enjoyed this article, please consider supporting our award-winning journalism. Currently subscribing. By subscribing, you help ensure future generations of influential stories about the discoveries and ideas that shape the world today.
(An edited transcript of the interview follows:)
How worried should the average person be about antibiotic resistance?
Many scientists I interviewed for this book said they are very worried that the next pandemic will be bacterial because we are losing our antibiotic armor. Ta. In 2019, I found a statistic that someone dies from an antibiotic-resistant infection every 15 minutes in the United States. I couldn’t understand that at all. And the coronavirus only made the situation worse, as people became sicker and more antibiotics were used. The United Nations says that if we continue with business as usual and do not find viable alternatives to obsolete antibiotics by 2050, we will begin to lose millions of people to infections. That’s a dire prediction.
What is causing this resistance? Overuse of antibiotics or reliance on a single type of treatment?
Resistance is an inevitable side effect of evolution. Organisms that we want to compete with always develop their own defenses. However, it is also true that we overuse antibiotics in medicine and agriculture. There is a lot of emphasis in the mainstream media on people demanding antibiotics they don’t need. But large-scale agriculture plays a much larger role. When cows, pigs, and chickens are given antibiotics, the antibiotics are excreted into the environment, where the drugs continue to cause harm. They kill certain soil bacteria, but not all. Therefore, successful mutants appear in soil and water. And they reach our plates, where we ingest them and get sick from it, with no viable treatment left. Hospitals are also breeding grounds for superbugs because they require sterile environments.
What solutions are scientists looking for? Where do bacteriophages fit into them?
Phages are viruses that infect only bacteria. Their biological machinery does not match the machinery of our cells, but it does match almost perfectly the machinery of bacteria. Viruses attach to bacteria, invade inside, multiply, and cause the cells to burst. Bacteria can develop resistance to the phages that prey on them, but evolution also allows phages to evolve more mechanisms to attach to bacteria. Phages and bacteria have evolved in parallel to each other for millions of years. There are trillions of phages in nature. Scientists working on them say they are an inexhaustible resource.
Another approach involves finding new antibiotics from nature as well. (Penicillin, the first naturally occurring antibiotic, was derived from a fungus.) But this took longer than finding the right phage, which is now difficult. Artificial intelligence can also be used to design antibiotics and synthesize them in the lab.
Do you think bacteriophages are currently receiving enough attention and investment?
I think we are finally reaching the forefront of science. Phages were first discovered in 1917, before antibiotics. In the 1920s and 1930s, phages had a truly spectacular moment. In some cases they were the only life-saving infectious disease treatments, and doctors almost all over the world used them fairly successfully. But then companies started marketing phages for things they couldn’t do (such as treating viral diseases, fungal infections, and allergies), and two prominent American doctors (Monroe Eaton and Stanhope (Bayne-Jones) decided that phages were too unpredictable to be of use. Shortly after, we got antibiotics, but we almost completely forgot about phages.
In Eastern Europe and the countries of the former Soviet Union, phages were always used in parallel with antibiotics, as antibiotics are difficult to produce. For example, in the USSR there was often a shortage of antibiotics, so doctors went to the river, found large quantities of phages, tested them in the laboratory, and used them. It was a different spirituality. In the US, we value convenience and stability. Antibiotics had a longer shelf life than phages. It can also be made into tablets. There was also no need to run a large number of tests to identify the target pathogen.
With the pressing problem of antibiotic resistance, even more money is being poured into bacteriophage research. In the early 2000s, pioneers told me it was impossible to get money. Things have been changing, probably in the last eight years or so.
Is it fair to say that desperation forced the FDA to consider bacteriophage therapy?
That’s not a bad word. I think the real turning point was the Tom Patterson incident. In 2015, Patterson, a researcher at the University of California, San Diego, Acinetobacter baumannii I was on vacation in Egypt with my wife Stephanie (Strathdee). Being a scientist herself, Stephanie started looking for alternative treatments and came across phages. Tom’s doctor was somewhat familiar with this concept and said he would try anything that seemed to work. So Stephanie contacted researchers at Texas A&M University and the Navy, and doctors eventually gave Tom a cocktail of antibiotics and phages (under a special FDA exemption) to kill the bug. .
I later learned that the FDA actually wanted to look into cases like Tom’s. Tom’s treatment worked (as a proof of principle) because his illness was very serious and his treatment was well documented. After that, the money started coming in little by little. When I was writing the book, there were 50 clinical trials. Now there are many more. They are all at different stages.
How far along are these trials and what hurdles are they facing?
It all starts with phase one, where only a small number of participants need to demonstrate that it is safe. The clinical trial process is time-consuming. There’s a reason for that. You don’t want to put something out there that might do more harm than good, right? So bacteriophages are still in a fairly early stage. I’m pretty optimistic that we’re moving in the right direction in the United States, but we don’t know how much time we have left. Some European phage researchers have told me that they feel our regulatory authorities need a better way to approve these treatments, not necessarily on an individual basis. Masu. In Europe, especially Germany, the rules are a little more lax.
Many of the bacteriophages currently being studied destroy stomach worms. Could phages be injected intravenously, rather than swallowed, to target a broader range of pathogens?
We don’t have solid knowledge about what’s going on inside our bodies. In any infection of the intestines or urinary tract, bacteriophages can be very widespread. Intravenously? That’s another story.
Do you feel that approval of phage therapy is ultimately inevitable, or could horrific side effects potentially derail the field?
I think people are working hard enough because there is no alternative. And people have side effects to antibiotics all the time, and the drugs are still on the market. Without them, things are even worse.
Generally speaking, if phages are prepared correctly, side effects are very unlikely. If phages are to be administered intravenously, the phage solution must be free of bacterial debris (something that the immune system can violently reject) and be really, really purified. Otherwise, the system may go into harmful shock. 100 years ago we didn’t have good technology to properly purify solutions, but today that doesn’t matter.
There is also the question of how far the immune system can track the phage itself (possibly limiting therapeutic efficacy). However, there is not enough information about this. For phages to work, they must kill the infection before the immune system can destroy it.
Could scientists genetically engineer phages with desirable properties, such as the ability to more easily evade the immune system?
You probably can. If we knew which genes to replace with which, we could design more powerful phages. Multiple phages can also be administered in a cocktail of sorts. Phages cannot be patented on their own because they are natural organisms, but if you tweak them or combine them with other ingredients, you may be able to patent your product, so genetic engineering is This is often attractive to pharmaceutical companies.
How can regulators speed up the process?
it’s complicated. I don’t write much about policy, but I imagine the FDA might regulate bacteriophages in the same way they regulate influenza vaccines. One of the problems with phage control is that phages evolve over time and even within the human body. How do we set the dosage given that they multiply in the body? We like to have things measured, but with phages it’s up to Mother Nature to do what she does. You almost have to trust it.