Steffanie, an infectious disease epidemiologist at UCSD, and Tom, an evolutionary sociobiologist and experimental psychologist also at UCSD, are a couple on vacation in Egypt. Tom becomes quite sick and soon is taken to a clinic in Luxor.
He does not improve, so he is subsequently flown to another hospital in Germany, where it is discovered that he is suffering from a pancreatic pseudocyst and is also infected with a multi-drug resistant strain of Acinetobacter baumannii. This is one of the most dangerous nosocomial (hospital-borne) pathogens. They begin administering meropenem, tigecycline and colistin—heavy duty, last resort antibiotics.
Tom is transferred to the intensive care unit at the Thornton Hospital in San Diego, where they have more experience with this bug. However, his condition worsens and he goes into septic shock and is put on a ventilator. A drain that had been placed in his pseudocyst slips, causing the A. baumannii infection to enter his whole body. He is placed in a medically-induced coma and his doctors wonder how soon he will need dialysis. He receives many other antibiotics, but to no avail. Tom is dying.
Steffanie is overwhelmed and begins a scientific search for an answer. She discovers several therapeutic alternatives to the use of antibiotics, only one of which she deems workable. This is a treatment that uses bacteriophages (viruses that can attack and kill bacteria). A phage is much smaller than a bacterium and can only be seen with an electron microscope.
After locating sources of phages and seeking approval from the FDA for an eIND (experimental investigational new drug), she and her colleagues begin the work needed to create a product that may save Tom’s life. The correct phages, in the case of A. baumanini, need to be type-specific. This means that they had to be matched to Tom’s bacterial isolate. They also had to undergo a difficult purification process, and since bacteria actually evolve during treatment, several different phages would be used.
Between the chapters, there are eight interludes that relate the often horror-filled hallucinatory recollections that Tom experienced throughout his ordeal.
The startling details of this medical adventure describe the first time an A. baumannii phage therapy was administered intravenously to a human being in North America, and likely will help propel the FDA into forming appropriate regulatory protocol.
The Perfect Predator is ultimately a happy story, and also a profoundly significant work because its details illustrate not only the result but the method of excellent and elegant science.
We are very happy to include Dr. Strathdee’s answers to to some of our questions.
32nd Avenue Books Toys & Gifts: How is a phage’s suitability determined?
Dr. Strathdee: First, it must be determined whether a phage can be found that matches the bacterial isolate. The bacterial culture is streaked on a petri dish and incubated so that the colonies can be visualized. The environmental sample (or purified phage) is added to the petri dish and incubated. If a phage is present that matches the bacteria, plaques are seen as holes in the agar. The plaques can be plucked out and added to a new bacterial suspension to expand it, before purification. Ideally, the phage is also sequenced to ensure that it is a lytic phage that kills bacteria, as opposed to temperate phage (sometimes referred to as ‘lazy’ phage that integrates into the bacterial DNA and ‘hits the snooze button’). Temperate phage is not ideal for phage therapy but if those are the only phage that can be found, gene editing can be performed to convert it to lytic phage.
32nd Avenue Books Toys & Gifts: Can you describe your plans for future research?
Dr. Strathdee: IPATH is engaged in research to determine optimal phage dosing and pharmacokinetics, as well as to move phage into clinical trials. We are also fundraising to develop phage banks of fully characterized phage for major superbugs that could be available on every continent.
32nd Avenue Books Toys & Gifts: Are phages obtainable for other AMR (anti-microbial resistant) pathogens?
Dr. Strathdee: Oh yes. Phage have been found for almost every bacterial species. Sometimes these are temperate phages that need genetic modification, as described above.
32nd Avenue Books Toys & Gifts: Do you see a time when humans will essentially be disease free?
Dr. Strathdee: No. I don’t think its realistic to try to purge our bodies of micro-organisms as some play beneficial roles. Bacteria and phage have co-evolved for millennia and the invisible arms race between them will continue. We need more research to understand how bacteria, phage and our immune system interact. We believe that phage can be developed to stay ahead of antimicrobial resistance, which means having large, ever-expanding phage banks available.
For more information, see https://IPATH.USCD.EDU and ThePerfectPredator.com.
Steve Brehm
32nd Avenue Books Toys & Gifts
