Lina Zeldovich is an award winning journalist and science writer. In this book Zeldovich discusses the use of bacteriophages (phages) - viruses that destroy bacteria - to treat infection and disease.
By now it's well known that 'the miracle of antibiotics' is over. Antibiotics are drugs that destroy bacteria, and antibiotics like penicillin once reliably treated gonorrhea, syphilis, tetanus, anthrax, gangrene, staphylococcus infections, streptococcus infections, meningitis, food-borne intestinal diseases, and so on.
As early as 1940, however, scientists were already seeing the emergence of bacteria resistant to penicillin. To address the problem, researchers developed new and stronger antibiotics, one after another, but bacteria ALWAYS develop resistance sooner or later. This is evidenced by infections such as methicillin-resistant Staphylococcus aureus, or MRSA. According to Zeldovich, "This dreaded superbug now lurks in hospitals, sickening 120,000 American per year and killing about 20,000. MRSA currently responds to vancomycin [used for the treatment of serious, life-threatening infections], but they may learn to repel it."
Staphylococcus aureus
Zeldovich describes an alternative treatment for bacterial illnesses, namely phages. Phages are special kinds of viruses that prey solely on bacteria. Phages look like tiny rockets, a thousand times smaller than their prey, which they pierce with their tails. The phages then reproduce inside the bacteria and burst them open.
Phages attacking a bacteria
The Soviet Union has been using phages to treat diseases for decades, but western countries have been reluctant to embrace this therapy. As Zeldovich notes, "Unfortunately, you can't yet buy a bottle of bacteriophage in your local pharmacy - not over the counter or by prescription. But in the era of skyrocketing antibiotic resistance, these phages might be our best weapons against the next bacterial pandemics."
Zeldovich provides a comprehensive history of medicinal phages, starting with Giorgi Eliava's discovery of bacteria-killing phages in 1917.
Georgi Eliava
Eliava was a trained microbiologist in the Georgian city of Tiflis (Tbilisi), studying the city's drinking water for disease-causing microbes. "And sure enough, there they were....Vibrio cholerae [cholera bacteria] that turned people into emaciated blue corpses, literally sucking their life out of them."
Vibrio cholerae
Patient with cholera
Eliava was examining a microscope slide containing contaminated drinking water, and saw Vibrio cholerae bacteria wiggling around. Eliava happened to leave the slide for a couple of days, and when he looked again, there were no bacteria on the slide. SOMETHING MUST HAVE KILLED THEM! It took some time, but Eliava discovered the 'something' was bacteriophages.
As often happens in science, another researcher also discovered phages in the early 20th century - Félix d’Hérelle, a scientist at the Pasteur Institute in France.
Félix d’Hérelle
D'Hérelle was studying Shigella dysenteriae, the dysentery-causing germs ravaging soldiers during WWI. A recovering patient had dying Shigella dysenteriae microbes in his stools, and when d’Hérelle seeded stool samples onto petri dishes, empty patches developed where Shigella had been destroyed. Once again, the killers were bacteriophages.
Shigella dysenteriae
Patient with dysentery
D’Hérelle became convinced the phages, which devoured specific bacteria, could be beneficial to people, to be curative entities and "agents of natural immunity." Other researchers began to experiment with phages, and their healing power was soon proven. Phages are especially good candidates for remedies because they're abundant in water, soil, and especially in sewage. Scientist Alexander “Sandro” Sulakvelidze, a phage expert, observed, "They are the most plentiful biological entities in any habitat, but sewage is particularly good for phage-hunting because it's teeming with various bacteria that become phage food."
Zeldovich goes on to discuss the development of phage 'therapies', which became ubiquitous in the Soviet Union and used in other places, such as parts of Africa, India, and the Far East.
Researchers developed phage therapies
The author also provides mini-biographies of scientists who studied phages, and Eliava's life in particular is fascinating. Zeldovich writes,"Gregarious and full of burning energy, Eliava embraced his city to the fullest. He instinctively knew how to dress, how to court, how to charm. He appreciated art and literature. He was a passionate dancer and an enthusiastic boxer. He cherished good food and had a sweet tooth. He rode horses [and was] a prankster always ready to pull a joke on a friend." Eliava married the beautiful opera star Amelia Wohl-Levicka, and at the height of his career - when Eliava was building the Tiflis Bacteriophage Institute (later renamed the George Eliava Institute) - the microbiologist tragically got caught up in Stalin's purges.
Amelia Wohl-Levicka
George Eliava Institute for phage therapy
Unlike Eliava, Félix d’Hérelle didn't have a degree in microbiology, but had a passionate interest in the subject. A "restless world traveler", d’Hérelle studied microbes wherever he went, and his wife Marie Caire was his lab assistant. At times, D’Hérelle worked with Georgi Eliava in Tiflis, and the two scientists traveled together, attended microbiology conferences, visited major research centers, and exchanged bacterial cultures and phages with other scientists. Unfortunately, d'Hérelle's travels exposed him to exotic germs, and he contracted amoebiasis (dysentery caused by amoebas) two times, and a long-lasting fever of unknown origin. All this led to d'Hérelle's chronic ill health later in life. D’Hérelle's lasting contributions to science include two important books about bacteriophages.
Entamoeba histolytica (an amoeba that causes amoebic dysentery)
Zeldovich writes about additional scientists as well, and it took a group effort to advance phage therapy. Nevertheless, phage medicines were a hard sell in the west, and "No average American clinician in the United States would try phages for treating bacterial infections."
This began to change in the early 1990s, when Glenn Morris at the University of Maryland offered Alexander “Sandro” Sulakvelidze, from the Soviet Union's Eliava Institute, a postdoctoral fellowship. Sandro informed Morris about phage therapy, and they put together a proposal regarding the use of phages to treat MRSA. There was TREMENDOUS pushback/criticism from American scientists and doctors, and the proposal was denied. However, in 2006, phages were approved for use in food safety.
Afterwards, in 2016, phage medicine was approved in the United States, on 'one-off' grounds, for a man called Thomas Patterson in San Diego. While vacationing in Egypt, Patterson had contracted a 'vicious bug' called Acinetobacter baumannii, which infects many organs and systems. Patterson had tried about fifteen antibiotics, been in and out of comas, and was on the brink of death. Luckily for Patterson, his wife Steffanie Strathdee was an infectious disease epidemiologist, and Strathdee reached out to every medical expert she could find. This led to phage therapy being approved for Patterson on a onetime basis with an 'experimental Investigational New Drug' (eIND). It took a global effort to produce the phage medicine, and it worked. Patterson recovered! After that, several other dying patients were treated with phages on an eIND basis.
Acinetobacter baumannii
Thomas Patterson and his wife Steffanie Strathdee
Finally in 2018, Sandro - who was now President and CEO of the biotech venture Intralytix, Inc. - was approved to do a clinical trial that involved growing phages to treat Crohn's disease, "a chronic inflammation of the gastrointestinal tract that causes pian, diarrhea, fatigue, weight loss, and malnutrition, and has no known cure."
Alexander “Sandro” Sulakvelidze
Crohn's Disease
Sandro then wrote proposals to test phages against other illnesses, all of which laid the groundwork for possible medical applications in the United States. So widespread phage therapy may be in America's future.
Zeldovich covers much more ground in her book, which I'd recommend to everyone with an interest in health and medicine.
Thanks to Netgalley, Lina Zeldovich, and St. Martin's Press for a copy of the book.
Rating: 5 stars
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