Muizelaar had devised the procedure in collaboration with a young neurosurgeon in his department, Rudolph Schrot. But as the consent form crafted by the surgeons, and signed by Egan and his wife, made clear, the procedure had never been tried before, even on a laboratory animal. Nor had it been approved by the Food and Drug Administration. The surgeons had no data to suggest what might constitute a therapeutic dose of Enterobacter, or a safe delivery method. The procedure was heretical in principle: deliberately exposing a patient to bacteria in the operating room violated a basic tenet of modern surgery, the concept known as “maintaining a sterile field,” which, along with prophylactic antibiotics, is credited with sharply reducing complications and mortality rates. “The ensuing infection,” the form cautioned, “may be totally ineffective in treatment of the tumor” and could cause “vegetative state, coma or death.”
For four weeks, Egan lay in intensive care, most of the time in a coma. Then, on the afternoon of November 10th, Muizelaar learned that a scan of Egan’s brain had failed to pick up the distinctive signature of glioblastoma. The pattern on the scan suggested that the tumor had been replaced by an abscess—an infection—precisely as the surgeons had intended. “A brain abscess can be treated, a glioblastoma cannot,” Muizelaar told me. “I was excited, although I knew that clinically the patient was not better.”
In Terri Bradley’s examination room, Muizelaar impulsively shared what he had just learned. “It escaped my mouth: ‘I just got this news about this treatment we tried on this one patient. Even though he is clinically not better, it appears that his tumor is disappearing. I think this might be your only chance.’ ”
But for decades talk has circulated in the field about glioblastoma patients who, despite hospitals’ efforts to keep the O.R. free of germs, acquired a “wound infection” during surgery to remove their tumors. These patients, it was said, often lived far longer than expected. A 1999 article in Neurosurgery described four such cases: brain-tumor patients who developed postoperative infections and survived for years, cancer-free.
Three of the patients were infected with Enterobacter, the fecal bacterium, and although the cases were anecdotal, and the alleged connection between the bacterium and survival was unproven, the notion became operating-room lore. One neurosurgeon, currently in private practice, told me that his former boss would joke during operations, “If I ever get a GBM, put your finger in your keister and put it in the wound.”...
(In 2009, in an attempt to put the wound-infection rumor to rest, neurosurgeons at Columbia University analyzed the records of nearly four hundred GBM patients, and found “no significant survival difference” between the vast majority who did not have an infection and the eighteen who did. However, a 2011 study of nearly two hundred GBM patients by researchers at the Catholic University School of Medicine, in Rome, found that the ten who had wound infections lived, on average, twice as long as those who did not.)
Young’s department had firsthand experience with a GBM survivor: a woman with a wound infection who lived for more than a decade. Muizelaar, who eventually took over her care, was fascinated. Cancer is notoriously deft at evading the immune system; he assumed that the bacteria in the woman’s brain had triggered an immune response that was eventually directed at her tumor, but he wasn’t especially interested in how that process might work. “I’m very practical,” he told me. “I only want to know whether something helps.”...
Muizelaar e-mailed a draft of Egan’s consent form to the hospital’s chief medical officer, and on October 11th, four days before the procedure, Schrot discussed it in a telephone call with Eric Mah, then the director of Davis’s I.R.B. Schrot explained that he wanted to treat a dying patient with live bacteria from his lab. (Although Schrot did not assist with any of the Enterobacter surgeries, he did much of the advance legwork and helped care for patients.) In a follow-up e-mail, Mah wrote, “I do not believe this requires IRB review as it does not qualify as human subjects research.” Nor, he went on, does the procedure fall under the F.D.A.’s authority, “because you are treating a single patient in the course of clinical care” and “are not trying to obtain the drug/biologic from an outside source.”...
After Terri Bradley, he said, “I didn’t intend to do any more patients.” On November 19, 2010, Bradley became the second patient to undergo the Enterobacter procedure.
Four days later, Patrick Egan died. He only fleetingly regained consciousness, and his family decided not to keep him alive through artificial means. An autopsy found evidence of cancer and infection. (“Very little tumor, practically all abscess,” Muizelaar said.) At the same time, Terri Bradley began to improve...
Within a few weeks, she was able to talk again, and a brain scan showed that the tumor in her speech area was shrinking. During the next several months, it disappeared, and the butterfly glioma shrank to the size of a dime. “I thought, Wow, these guys are good,” Janet Bradley recalled. “They’re going to figure it out.” The surgeons were also excited. “This woman should have been dead,” Muizelaar said. “Her speech got better, and one of her two tumors disappeared. It was incredible.”...
The woman’s tumor was “so massive and deep in her brain, we knew we couldn’t completely resect it,” he told me. But Terri Bradley’s response had emboldened him. Never before had he offered the therapy to a newly diagnosed patient, who had yet to pursue the standard treatment for the disease...
According to Smith, as he walked into the room he announced, “I’ve got egg on my face. Our third patient is not doing well—she is going to die.” After a brief discussion, the meeting was adjourned. “It was understood by everyone there that this was stopping,” Smith said....That morning, the third Enterobacter patient died, of a stroke, after intravenous antibiotics failed to reverse her decline. “The infection overwhelmed her brain,” Muizelaar said...
By then, Terri Bradley was dead. Despite the remarkable brain scans early on, her physical recovery faltered. She remained lethargic and partially paralyzed, and had trouble forming words. The oozing wound in her skull emitted an unbearable stench. “Walking into that room, I felt so bad for her roommate,” Janet said. “I’ve never smelled anything worse in my life.”
In October, 2011, Muizelaar and Schrot finally decided to treat Terri’s Enterobacter infection, by removing her bone flap and flushing the wound with antibiotics. A month later, she died. She had lived for a year and a week after the wound-infection procedure, but to her daughters the achievement felt hollow. “It was miserable for her,” Janet said. “She had no quality of life.” Whether the treatment worked, Muizelaar had no way of knowing. But it did not help.
Courtesy of a colleague
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