Cobbs had observed that his patients diagnosed with malignant glioma - an aggressive brain cancer that leaves victims with a two-year life expectancy - were mostly older, well-educated and from higher socioeconomic backgrounds.
Their "hyper-hygienic" lifestyles had possibly left their immune systems susceptible to more common viruses, such as the human cytomegalovirus, or CMV, a herpes virus so ubiquitous that it infects 4 of 5 Americans.
During off-hours, and without formal research funding, Cobbs and a lab partner analyzed dozens of brain tumor samples: All of them were riddled with CMV.
In 2002, the doctor published his novel finding in a leading medical journal Cancer Research where it was quickly dismissed by many of his peers.
"I was left with a lot of self doubt," said Cobbs, now 45. "My fear was that we'd done something incorrect. But now, my confidence is growing."
In February, brain cancer researchers at Duke University Medical Center published the first peer-reviewed report that confirmed Cobbs' discovery, followed by two reports from independent labs at the M.D. Anderson Cancer Center at University of Texas in Houston and the Karolinska Institute in Stockholm, Sweden. And this month, the National Brain Tumor Society is sponsoring a first-of-its-kind gathering in Boston of the world's top virologists and glioma experts to examine the possible link between CMV and the deadly brain tumors that are diagnosed in 10,000 Americans every year.
"His discovery opens the door and has broad implications in this field," said Dr. Duane Mitchell, a Duke University Medical Center researcher who is conducting vaccine trials based on Cobb's findings. "And the door has just been opened."
An unorthodox connection
Cobbs came up with the idea to connect CMV and brain tumors while reading "Surely, You're Joking Mr. Feynman!" a collection of reminiscences on the value of original thinking by Nobel Prize-winning physicist Richard Feynman. The book inspired Cobbs to re-examine long-held assumptions in his field.
Medical researchers have long known that CMV exists in a latent state for most people unless a person's immune system is compromised. While it's a common and unremarkable virus in some ways, CMV also causes persistent infection and is known to carry cancer-causing properties. It's also the most common cause of congenital brain infections in humans, according to the Centers for Disease Control and Prevention.
Cobbs expected another researcher had considered CMV as a likely culprit for brain tumors, but he found no published evidence.
"When I stopped to think, 'If I was going to cause a brain tumor, what would I be?'" Cobbs said, "CMV made a lot of sense. ... But if you tell people you think like that, in these days of rigid grant proposals - well, it might not win you that research grant."
A response to Cobbs' initial findings in a 2004 issue of the journal Modern Pathology arrived from City of Hope researchers in Southern California that was particularly authoritative. The group studied 22 brain tumors and concluded that "none demonstrated evidence of CMV."
But Cobbs and his lab assistant had invented a more thorough technique to search for the virus, called antigen retrieval, which made the testing methodology 10 times more sensitive, with the result that the antibodies could more easily "see" the virus.
Cobbs said he offered to demonstrate the antigen retrieval technique to City of Hope researchers, but they declined to meet with him. They also did not respond to an interview request for this article.
Extending patients' lives
For the researchers who have confirmed Cobbs' methods, action is already under way. Mitchell, the Duke researcher, started a trial two years ago with 13 patients using a vaccine against the virus that stimulates the immune system to attack the infected tumor cells.
One of the desired results of such antiviral treatment is to thwart the return of cancerous tumors once they've been removed. Currently, according to the National Brain Tumor Society, about 95 percent of patients whose tumors were removed and who underwent chemotherapy and radiation treatment saw a tumor return in six to eight months.
Several of the patients in the Duke trial were tumor-free after two years, but Mitchell would not give specific data about his patients, which he is compiling for publication in a peer-reviewed journal. About half were just now seeing a return of the tumor, he said.
Doctors for Sen. Edward Kennedy, who was diagnosed with glioma in May and operated on at Duke, would not confirm whether he is participating in the anti-CMV drug trials at the university.
In San Francisco, some of Cobbs' patients who are taking Valcyte, an anti-CMV drug are experiencing results similar to those of Mitchell's patients.
Francis Gates, 81, who had a golf-ball-size tumor removed one year ago, only recently has seen signs of returning growth. Gates, who grew up in the rural Placer County town of Loomis, and worked as director of law libraries at University of Southern California and Columbia University, has undergone chemotherapy and radiation treatments in the past year in addition to taking Valcyte. Although he is unsure if his early life growing up on a farm matched the hygiene profile Cobbs had observed among glioma patients, he would not rule out the theory. He is also unsure if the antiviral drug is responsible for suppressing the tumor growth and extending his life, though he's thankful he's lived longer than doctors estimated.
"I feel lucky," Gates said. "But I've also felt that way my whole life. I just try to focus on my quality of life today, and see if I can't have some fun along the way."
Hopes for treatment, funding
During a recent two-hour surgery at California Pacific Medical Center on Castro Street, Cobbs removed a knot of infected brain tissue from an 83-year-old female patient and quickly dropped it into a vial held by Liliana Soroceanu, a neuroscience brain tumor researcher who then drove the tumor across town to their South of Market lab.
While Cobbs gathers research, removing roughly 100 tumors a year, it's still unknown how his CMV-related discovery will translate into treatment, especially for older patients, said Dr. Susan Chang, director of the Division of Neuro-Oncology at UCSF.
"There's still a number of questions to be answered as to what kind of treatments this discovery will lead to," Chang said, "and which patient populations might benefit most. Will this work best for older patients? Or only young patients? We're still not sure, and that's what we'll start discussing at the symposium."
The Boston gathering has been described as somewhat unusual by Cobbs' peers. Rarely is a surgeon able to gather so many top thinkers and researchers from multiple fields to discuss a theory that is not yet widely accepted by the medical establishment.
He hopes the event will also kick-start a critical mass of acceptance, so that funding will follow.
"We'll get the skeptics together, have a meeting, brainstorm and see if this is worth pursuing," Cobbs said.
"It's almost been taboo because no one wants to stick their neck out on this," he said referring to virologists and pathologists. "But I have nothing to lose. I'm just a surgeon."
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This article appeared on page A - 1 of the San Francisco Chronicle