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Defying odds on brain cancer, and inspiring students

Tim Lynch has a theory about why he beat the brutal brain cancer glioblastoma. Even with intensive treatment, the average survival is about 15 months. As the tumor grows, it destroys the very abilities that define people as human - thinking, feeling, communicating.

Twenty-three years ago, Timothy Lynch fought glioblastoma, the fearsome brain cancer that usually kills within two years. Now the Penn Charter School biology teacher is working with University of Pennsylvania researchers to try to figure out why he beat it. ( DAVID SWANSON / Staff Photographer )
Twenty-three years ago, Timothy Lynch fought glioblastoma, the fearsome brain cancer that usually kills within two years. Now the Penn Charter School biology teacher is working with University of Pennsylvania researchers to try to figure out why he beat it. ( DAVID SWANSON / Staff Photographer )Read more

Tim Lynch has a theory about why he beat the brutal brain cancer glioblastoma.

Even with intensive treatment, the average survival is about 15 months. As the tumor grows, it destroys the very abilities that define people as human - thinking, feeling, communicating.

Brittany Maynard, who at age 29 became the face of the right-to-die movement, was so determined to cut short the inevitable horror that she ended her life with a lethal prescription this month in Oregon, 10 months after her glioblastoma diagnosis.

Incredibly, Lynch was diagnosed 23 years ago; only three other 20-year survivors have been documented. Now 47, he is an esteemed biology teacher at William Penn Charter School, where his own two children are enrolled. His students call him "Doc," a nod to his doctoral degree and his rapport with them.

The only visible reminder of his cancer is a deep, uneven indentation, about three inches by four inches, on the right side of his shaved head. He opted for the cue-ball look when male pattern baldness merged with radiation-ruined follicles.

"My 10-year-old son recently said, 'Dad, when I was little, why did you lie to me and say you fell off your bike and that's why I need to wear a helmet?' " Lynch said, sitting at his wooden desk in the Penn Charter office he shares with another teacher.

Lynch's theory about his longevity involves the fluky postoperative complication that left him with his dented pate. But another explanation occurs to doubters.

"The first thought everyone has is, he must have been misdiagnosed," said Maria Martinez-Lage, a neuropathologist at the University of Pennsylvania. "That was my first reaction when I met him."

This year, in one of the fortunate twists that have punctuated Lynch's life, glioblastoma became a way to unite the scientist and the survivor. He spent six months, through August, on sabbatical at Penn, in the lab of Nadia Dahmane, a neurosurgical researcher.

They did tests that confirmed his diagnosis. They also began tumor analyses that are yielding insights into glioblastoma's formidable ability to hijack the body's immune defense system - insights that tie into Lynch's theory about why he is such an outlier.

Initial seizure

Lynch was a 23-year-old Skidmore College graduate when he had his initial grand mal seizure.

It was New Year's Eve 1990, his first night in Burlington, Vt. He was embarking on a teaching fellowship - the classic path to a doctorate - in the University of Vermont's botany department.

An EEG test and a CT scan at the University of Vermont Medical Center showed nothing. The emergency room doctor implied Lynch had suffered a side effect of partying.

Over the next six months, the seizures worsened. Lynch's parents, at home on Long Island with his younger siblings, grew frantic.

Finally, Lynch's doctors tried a then-new brain imaging technology - MRI. It revealed the tumor in the rear of the frontal lobe, near a region crucial to voluntary movement.

Based on that location and Lynch's age, Paul L. Penar, a neurosurgeon at the medical center, guessed the tumor was a relatively slow-growing "astrocytoma," the most common type of brain cancer diagnosed in children and young adults.

"I thought it didn't appear that aggressive on the MRI," Penar recalled.

Lynch consulted neurosurgeons far and wide, but stuck with Penar's team because, fortuitously, it was at the forefront of using new brain-mapping technology to avoid the crippling effects of indiscriminate tissue removal. By stimulating Lynch's arms and legs during the operation, the surgeons were able to identify and preserve vital nerves while still achieving maximum tumor reduction.

But the golf ball-size malignancy was not astrocytoma.

"Three days after surgery, the pathology came back," Lynch recalled. "Dr. Penar told me I had nine months to live. My whole family was there. We were devastated."

To his mother's anguish, Lynch refused to move back to Long Island. Throughout six months of radiation and chemotherapy - of "puking and feeling horrible" - he soldiered on in graduate school.

"I wanted," he said, "to keep my brain busy."

Glioblastoma usually comes roaring back, but every three months, Lynch exulted when his MRIs showed no recurrence. His only setback involved the patch of skull bone that had been cut out and reattached; "pimples" appeared on the scar line. Penar drained the persistent but seemingly minor infection, and prescribed an uncomfortable antibiotic-saturated dressing.

Then, 15 months after his brain surgery, Lynch slipped and hit his head, breaking the abscess open.

Reluctantly, Penar decided the infected patch of bone was beyond salvaging. In the operating room, he discovered the infection had also penetrated Lynch's dura - the thick protective membrane of the brain - and caused some brain inflammation.

The neurosurgeon was the first to speculate that this potentially fatal complication had an ironic benefit: As Lynch's immune system battled the raging infection, it attacked remnant glioblastoma cells.

"I do have a sense that the infection helped treat the tumor," Penar said. "Some neurosurgeons are starting to pay attention to the theory."

Indeed, in 2011, Italian scientists bolstered what they called "the prevalent myth" about postoperative infection. They found that 10 glioblastoma patients who developed it survived a median of 30 months, twice as long as 187 patients with no infection.

At the University of California, two prominent neurosurgeons went further, intentionally putting bowel bacteria into three glioblastoma patients who consented to the desperate gambit. Two patients died within weeks; one survived more than 12 months. The doctors resigned last year amid the resulting scandal.

Following his bliss

In 1997, Lynch donned the velvet-trimmed robe of a Ph.D. His published research elucidated how plants sense gravity and send growth signals. It is cited in two popular college biology textbooks.

Although he was happy doing basic research, he soon realized that the relentless quest for funding would make him miserable. If cancer had taught him anything, it was to follow his bliss, or at least avoid glumness. So he decided to pursue his other passion, teaching.

Since he didn't have formal teaching certification - unlike his wife, whose job in Upper Dublin schools led them to move to Cheltenham - he applied at Penn Charter, the storied private Quaker school in the city's East Falls section.

"We saw Tim would be a perfect fit," headmaster Darryl Ford recalled.

Actually, Lynch had to cancel his interview because of a seizure, but the woman who was hired changed her mind. He joined Penn Charter in September 1998.

He is the first to say he has a dream job. The 325-year-old college-preparatory institution on a fabulous campus attracts the best and the brightest.

Even so, by all accounts he makes them better.

Joya Ahmad, 21, now a Columbia University biomedical engineering major, credited Lynch when she became a 2011 U.S. presidential scholar. Only 141 high school seniors out of three million are selected for the annual awards.

"Entering high school, science bored me," Ahmad said at the awards banquet in Washington, attended by Lynch. "Doc revealed the science behind everything - the blink of an eye, the detonation of a bomb, the swing of a bat. Science, Doc taught me, is life."

Matthew Nazarian, a student at Jefferson University's Sidney Kimmel Medical College, remembers Lynch as a nurturing stickler who collected 25 cents for charity every time a student said "like."

"If you were rude or disrespectful, he would make you come in and get gum off the desks, or feed the turtle," Nazarian said. "Those were good lessons."

On the first day of classes, Lynch lays out his cancer history and what to do if he has a seizure. Thanks to medication, that's never happened, but the safety talk builds trust.

"I want it to be like a family," Lynch said. "You're talking about sex, genetics, disease, drugs. These are all things we speak about in the context of biology. By the end of the second month, that family starts to solidify."

It was while accompanying a student on a tour of Penn's neuroscience labs in February that Lynch saw an opportunity for himself. He wanted to learn new molecular analytical methods to augment his lesson plans. He also hoped to use his own tumor sample - still preserved in Vermont - to find genetic markers of long-term survival.

Both Penn Charter and the neurosurgery department heartily supported his sabbatical proposal.

"He is a scientist at heart," Dahmane said.

Brain's defense system

Researchers used to believe the brain was devoid of normal immune function because it has a unique barrier that blocks most immune cells - and, alas, chemotherapies.

Now, though, it's clear that the brain has a distinctive defense system that may be a promising therapeutic avenue. In particular, it has a resident population of Pac-Man-like cells called macrophages. They gobble up dead cells and pus - as in Lynch's abscess - and form the first line of defense, activating armed immune soldiers.

Lynch and his Penn collaborators wondered: Could the numbers of macrophages and other immune cells in tumor samples be correlated with the length of patients' survival? Could the intensity of an immune system brake - a protein called PDL-1 that is slammed on by tumors - be correlated with survival?

Although they're still analyzing data to answer the first question, the answer to the second is a qualified yes. They found that in two of four subtypes of glioblastoma, the more PDL-1 activity, the shorter the survival.

That finding already has treatment implications. As Lynch knew while helping to evaluate tumor samples from 56 patients, immunotherapies are being developed that cut the PDL-1 brake. One company's drug is already approved and being clinically tested in glioblastoma patients.

And what about Lynch's own brain cancer?

He rattled off the four genetic mutations - a gibberish of letters and numbers to the layman - that Martinez-Lage identified in his aged tumor sample. (His sample was not part of the larger analysis.)

Three of the mutations are proven drivers of glioblastoma. The fourth is found in "secondary" glioblastomas - the 10 percent that arise from less-aggressive astrocytomas, the tumor Penar expected to find.

"It explains a little of why he survived longer, but still not the 20 years," Martinez-Lage said. "People with secondary glioblastoma live on average six to 12 months longer."

For Lynch, who continues the Penn collaboration one day a week, deciphering the destroyer that somehow spared him has been an affirmation.

"In some small way, I feel I've contributed to finding a cure," he said. "Maybe it's a minuscule contribution. But I've survived, and I felt it was almost an obligation to my friends who've passed to try to help figure this out.

"The impact on the kids," he added, "is, they see a real researcher teaching them. I'm still in the game."

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