Dr. Linda Liau stands outside the neurosurgical operating room at UCLA on an August morning, amiably talking with her husband about who is going to pick up the kids after school. Her spouse, Dr. Marvin Bergsneider, is also a UCLA neurosurgeon, and he says he has a meeting to attend, to which Liau, jabbing with her thumb over her shoulder toward the operating room, responds, “Yes, but I have a brain surgery to do.” Brain surgery trumps meeting, and 15minutes later, Dr. Liau, having resolved the minutia of everyday family life, is scrubbed and standing over a patient’s open skull preparing to save his life.
On average Liau operates about four times a week — two-a-day on Mondays and Thursdays. One day a week, she’s in clinic. One week out of every six, she is on 24-hour call for emergencies, and she’s the editor-in-chief of a prestigious academic publication, the Journal of Neuro-Oncology, which she works on at home, between 9 p.m. and 2 a.m., when her children, Bianca, 8, and Brendon, 11, are in bed.
And the rest of the time? Between meetings, rounds, responding to e-mails and collaborating with other physicians and postdoctoral fellows on various projects, Liau has made her mark as a pioneering scientist, working in her laboratory at UCLA’s Jonsson Comprehensive Cancer Center to refine a promising new vaccine that is custom-tailored to each patient to thwart the recurrence of brain cancer once it has been surgically removed. The vaccine is compounded from the patient’s own tumor and immune cells and is now undergoing its third clinical trial and showing remarkable promise. For some of the patients in Liau’s studies, the vaccine has added months, even years, of life for those with a disease that is frequently, and often quickly, fatal.
To manage all this, Liau averages about four hours of sleep a night, “which for me is plenty,” she says, although she does admit to being a little grumpy when she first wakes up in the morning.
In a field dominated by men, Liau’s reputation as a surgeon and scientist is international. She is, say colleagues, among an elite handful of neurosurgeons who are leading the way in translational research —taking science from the bench to the bedside to find new and more effective therapies for a terrible disease. And in addition to being a gifted surgeon and innovative researcher, Liau is an inspirational educator and mentor for the next generation of clinician-scholars,” says Dr. Joseph Piepmeier, vice chair of neurosurgery at Yale University School of Medicine and Liau’s predecessor as editor of Neuro-Oncology.
Although there have been many job offers, Liau elects to stay at UCLA, where she received her neurosurgical training and earned a doctorate in molecular neuroscience, and her patients are grateful. Many have come to Los Angeles from other parts of the country after learning about her from their own independent research.
That is how Dominic Bakewell, the patient on the table inside the UCLA hospital operating suite that August morning, found Liau. A singer-songwriter who played guitar for a time with the New Wave band Berlin in the 1980s, Bakewell was at home in 2006 with his 2-year-old son, Julian, when he had a seizure that left him unconscious. An MRI at a nearby emergency room failed to reveal a problem. It was not until he had a second seizure a month later, and a second brain scan, that his diagnosis was made — a tumor had formed on the left frontal side of his brain. When Bakewell and his wife started looking for the best surgeon they could find, they were quickly attracted to Liau. She was young, she was cutting-edge and she was a researcher as well as a surgeon. She was not just excising tumors; she was looking for ways to stop them in their tracks.
But when Bakewell and Liau met, the news was not good. The tumor’s location was problematic. Prior to meeting Liau, neuropsychologists at UCLA’s Brain Mapping Center had scanned Bakewell’s head to identify the critical regions in his brain that control speech and motor movement. In Bakewell’s case, the tumor was pressing against the motor and speech areas of his brain. It was devastating enough to be diagnosed with a brain tumor, but for a guitar-playing singer and songwriter, the news made things much worse.
And as detailed as the brain map is, there is no clear demarcation in the brain that says speech is here and motor ability is there. Cut a little too much this way or that way, and Bakewell could lose his ability to speak. And then there’s the standard complications that are always a possibility with any surgical assault to the brain — bleeding, allergic reaction to medications, infections, seizure, stroke, paralysis, loss of sensation — the list goes on. Bakewell’s surgery was risky business.
It was her mother’s death from cancer that inspired Liau to pursue her current course. Her mom had long been Liau’s chief cheerleader, encouraging her that she could do whatever she wanted to do in life. Liau was in the third year of her residency at UCLA when her mother was diagnosed with cancer that had started in her breast and spread to her brain. Her mother died a short time later. She was just 51.
“After her death, I was angry as well as heartbroken,” Liau said. “I remember thinking, ‘Why hasn’t there been more progress with this disease?’”
It was the motivation for her to begin a dual-career path as a surgeon and a researcher, and it had a positive side effect. “Doing lab work helped me deal with the emotional aspects with regard to my patients. It makes me feel better, because I feel that I am contributing to knowledge about this disease,” she said.
Her dedication in both the operating room and the lab has made Dr. Liau, in the words of one admiring colleague, “the classic triple-threat.” “She is an innovative and caring physician; a superb teacher, mentor and example; and an investigator of international renown,” said Webster K. Cavenee, a scientist and director of the Ludwig Institute for Cancer Research at the University of California, San Diego.
As Bakewell is wheeled into the operating room, following an emotional, tear-filled parting from his wife, Sarah, Liau and her colleagues are preparing to perform a procedure that only a handful of medical centers in the United States offer: an awake craniotomy. The patient, a section of his skull sawed open and his brain exposed, is brought out from under anesthesia and awakened to ensure critical sections of the brain are not removed. It is possible to do this because the brain has no pain receptors. And it’s a key surgical strategy when a tumor like Bakewell’s is pressed tight against the speech and motor centers.
Once the chunk of Bakewell’s skull is taken out and a palm-sized area of brain revealed, Liau goes to work. Over the course of several hours, she cuts out as much of the tumor as she safely can, based on what the multiple brain images show her. Finally, she is as close as she can get to the borderless margin where tumor and healthy brain intersect. It is time to wake Bakewell. Neuroanesthesiologist Dr. Barbara Van De Wiele carefully lightens Bakewell’s sedation. The first thing a foggy Bakewell does is cry out for his wife.
“Dominic, it’s Susan. Can you hear me? You are in the operating room. You are waking up.” Susan Bookheimer, a professor of psychiatry and member of the Brain Mapping Center, says to Bakewell.
She leans in closer: “Dominic, I need you to open your eyes and be very still.”
Using a grid developed from the brain map as her guide, Liau begins to probe Bakewell’s brain, trying to define the border between the tumor and the cells that control Bakewell’s ability to speak. Liau uses an electrified wand to touch the surface of the brain to temporarily short-circuit the ability of Bakewell’s neurons to communicate. At the same time, Bookheimer holds up a flashcard inches from Bakewell’s eyes. On it is a picture of a cat. As long as Liau stimulates those verbal cells to block their neural activity, Bakewell is unable to remember the word for cat. He knows what it is; he just can’t think of the right word.
When Dr. Liau lifts the wand, stopping the current, Bakewell responds. “Cat,” he whispers.
Liau uses the wand to touch a different area of his brain. Bookheimer holds up another card, a house. Bakewell can’t think of the word until Liau lifts the wand. And so it goes. Stimulate. Picture. Answer.
When Liau stimulates a part of the brain and Bakewell can still respond, she knows she can safely slice away at the tumor without doing damage. Finally, at the end of a tiring six-hour surgery, Bakewell is put back under anesthesia, and his skull and scalp are replaced.
It has been three years since Bakewell’s surgery, and he’s doing well. After therapy and hard work, he is singing and playing guitar again, and enjoying life as a husband and father. Last year, he released an album of children’s songs. Every three months, he undergoes a nerve-wracking MRI to check for any new tumor growth; so far, his brain is clear.
“I’d like to thank Dr. Liau for saving my life,” Bakewell said.
Liau was young when she started working on a brain cancer vaccine in 1998. At the time, she was a 31-year-old assistant professor, working with Dr. Michael Roth, a professor of medicine in the Division of Pulmonary and Critical Care Medicine, and Dr. James Economou, a professor of surgical oncology and molecular and medical pharmacology. Both were working on vaccines — Roth on cellular vaccines for lung cancer, Economou on immunotherapy for melanoma.
“It was certainly not a eureka! moment,” Liau said. “It was more just a question that came to me. If it could possibly work for lung cancer and melanoma, why not brain cancer?”
While Liau has refined her brain cancer vaccine over the years, the process by which it is made has remained basically the same, with each vaccine custom made for each eligible patient. Liau’s lab first extracts proteins from the patient’s tumor, then extracts the patient’s dendritic cells from their blood. Dendritic cells are a special type of cell essential for the start of any immune-system response. The dendritic cells are then loaded with extracts of the tumor cells and injected back into the skin of the patient, where they behave as if they just encountered an infection: They travel to the lymph nodes to “tell” the immune system about the tumor cells. The ensuing activation of the immune system results in the generation of killer T-cells that travel through the body. When these cells encounter a tumor cell, they kill it. The goal, Liau said, is to make a clean sweep of whatever cancer cells are left behind after surgery.
What makes glioblastoma so lethal is the speed at which it grows and sends microscopic shoots into different areas of the brain. Even the most talented neurosurgeon can’t excise a complete tumor cell by cell by cell.
Is the vaccine working? Liau has patients who have lived four and five years beyond the expected 18-month life span for glioblastoma. One has survived nine years. These are the lives that fuel Liau’s efforts. But developing a vaccine is an excruciatingly slow process. But Liau soldiers on. She is careful to tell each of her patients the “what-ifs.” The tumor may always come back, “maybe next week, maybe in five years.” Still, she is cheered by the number of patients whose lives she has extended.
“It does make me feel good. I do tend to get involved in the lives of my patients. They are, as a group, nice people leading interesting lives — musicians, firemen, doctors. But I really hope we can find a cure.”
Yet, always hovering over everything is the sobering realization that the cancer still wins. Last August, Liau lost one that really hurt. Kevin Carlberg was a father and husband, a musician like Bakewell, and a Liau cheerleader. He raised money for her research, he spoke of his experience to media, he wore a “Don’t worry, be happy” T-shirt to every medical appointment. He never gave in. He was a five-year survivor, and in that time he married, had a child, ran a marathon and cut a CD of his music.
And it was Liau, surgeon and scientist, who gave him those precious, extra years.
By Mark Wheeler, UCLA Medical Magazine, 2009