Battling Brain Cancer as a Neurosurgeon and Scientist
The challenge. Keith L. Black is no stranger to challenges. At age seven, he took on segregationist rules in his hometown of Auburn, Ala., by swimming in a “whites only” pool. Science became Black’s next challenge when he was a teenager. At 17, he published a paper based on his work in a heart research lab that won the national Westinghouse Science Talent Search competition.
So when Black graduated from the University of Michigan Medical School’s accelerated program at age 24, it came as no surprise that he chose neurosurgery as his specialty. And within that notoriously difficult field, he decided to “do battle”1 with the most malignant of all brain tumors—glioblastoma multiforme, or GBM.
An estimated 24,620 Americans are diagnosed with a malignant primary brain tumor every year, according to the American Brain Tumor Association. Almost half of those will have GBMs. GBM spreads “like wildfire,” Black notes, and is extremely difficult to treat because it infiltrates healthy brain tissue, reappearing in distant locations that make the tumor virtually impossible to completely remove surgically. Over the decades, Black attacked this problem both as a surgeon and a scientist.
The Harold Amos Fellowship. In 1987, Black received a four-year research fellowship from the Harold Amos Medical Faculty Development Program of the Robert Wood Johnson Foundation (RWJF). For more information on the program, see the Program Results Report. He had completed his residency at Michigan and was an assistant professor of neurosurgery at the University of California, Los Angeles (UCLA), Medical Center. His early research focused on one of the most formidable obstacles to treating GBM, the blood-brain barrier. This dense mesh of capillaries protects the brain but also prevents chemotherapies and radiation from reaching a malignant tumor. Black pioneered research on designing ways to open the blood-brain barrier, enabling the delivery of chemotherapeutic drugs directly into a tumor.
The Amos fellowship came at a critical time, according to Black. “A challenge that a lot of young faculty have—especially in surgical specialties—is to get protected research time to launch a career. It’s easy to get busy clinically. You need to have enough time to get a foundation of research.”
Black says the fellowship gave him both a “boost of confidence” and practical experience in putting together a research grant. Because Black was able to get RWJF support right after completing his residency, he was able to accumulate enough preliminary data to be in a “very competitive position” to apply for and secure a National Institutes of Health (NIH) grant in his first year at UCLA.
Changing direction. Over the next decade, Black’s academic reputation grew. By 1997, he held the Ruth and Raymond Stotter chair in the department of surgery at UCLA and was a professor in the neurosurgery and neurology departments. Black then accepted the opportunity to lead the newly formed Maxine Dunitz Neurological Institute at neighboring Cedars-Sinai Medical Center. According to Black, “Cedars wanted to deploy resources to help translate science from the lab to patient care. Unlike a traditional academic medical center, Cedars was willing to take revenue generated in the clinic and pour it back into research.”
In 2007, Black accelerated his fight against GBM and opened the Johnnie L. Cochran, Jr. Brain Tumor Center at Cedars-Sinai, named for the renowned defense attorney who developed GBM and was a patient of Black’s as well as a close personal friend and a longtime supporter of Cedars. “I regretted that I wasn’t able to do more for him at the time,” says Black, so after Cochran’s death, “we redoubled our fundraising efforts” with help from Cochran’s widow and a group of prominent donors known as the Brain Trust.
An array of scientific research. Black has published more than 260 peer-reviewed scientific papers on a wide variety of research projects. These include:
- An anti-cancer vaccine. Black has been “very focused over the last 20 years in trying to activate an immune response against malignant brain tumor.” His team has created various forms of a vaccine that takes dendritic cells from the patient’s blood and “loads” them with antigens—including tumor cells obtained during surgery.
“Dendritic cells,” says Black, “are the immune system’s most effective ‘presenting’ cells for things in our body that need to be attacked and eliminated.” The dendritic cell vaccine is “as close as we have been able to come to the ‘anti-tumor juice’ we dreamed about when I was still at the University of Michigan.”
Currently, Black is working with a start-up company, Immunocellular Therapeutics, to test a form of the vaccine called ICT-107. In a Phase 1 trial, 16 patients newly diagnosed with GBM received the vaccine. After five years, eight of the patients were alive with no evidence of tumor. These results are “quite spectacular,” says Black, as “five-year overall survival is only 5 percent to 15 percent.”
A Phase 2 clinical trial is now underway at 25 medical centers, with 127 patients randomized into two groups, one receiving the vaccine and the other a placebo. Preliminary results, reported in December 2013 after half of the patients had died, showed that survival was increased by three months in the treated group. Data collection continues, and Black remains positive that overall survival may show statistical significance.
- Penetrating the blood-brain barrier. Black oversees a lab supported by an NIH grant that uses nanotechnology to break through the blood-brain barrier. The lab has created a drug—called a nanobioconjugate—that is given by intravenous injection and is engineered to permeate the tumor cell wall.
- Early detection of Alzheimer’s. The protein plaques that accumulate in the brains of Alzheimer’s patients also form in the retina in the back of the eye where they can be seen even before they accumulate in the brain. According to Black, his team has “created an investigational device that allows us to look into the eye—just as an ophthalmologist does to diagnose retinal disease—and see these plaques. The device may potentially be an early index to detect people that are developing the disease before they are symptomatic.”
- Locating tumors during surgery. With support from the Dunitz Institute, Black is developing “smarter surgical instruments that focus a nonharmful laser on the tumor and can distinguish in less than a second between tumor and normal tissue. It’s a way to locate a tumor in real time, reducing the need for biopsy confirmation.”
Surgeon’s perspective. Black is as busy in the operating room as he is in the lab. Since 1987, he has performed more than 6,000 brain tumor operations. A good neurosurgeon needs “more than good hand-eye coordination and being well versed in neuroscience,” says Black. It takes “empathy for patients, but it’s also important to actually see ahead of yourself, to realize your mistakes intuitively before they happen, very much like a basketball player seeing the floor.”
No matter how skilled the surgeon, however, the brain remains a mystery, Black allows. “We know something about the basic biology of the brain, but how it truly works, how we experience consciousness, we haven’t even started down that path yet. The brain is sacred territory. We need to be very deferential. I describe it as being a thief in the night, sneaking into the brain to steal the tumor while leaving healthy tissue untouched.”
Mentoring the next generation. Black is an advocate for improving access to medical careers for disadvantaged kids. His program Brainworks, at Cedars-Sinai, introduces 7th- and 8th-graders to careers as physicians and researchers.
“One of real challenges of kids growing up in educationally disadvantaged areas—I’m using a new term here—is that they don’t have a chance to see what the potential is for careers in science. Brainworks is very small effort to stimulate students early, to keep them inspired, show them the magic of medicine and science.”
Through Brainworks, Black and his colleagues give talks to groups of 150 kids at a time. “I try to give a few little pearls to take away about what it means to be scientists.”
RWJF perspective. The Harold Amos Medical Faculty Development Program is a four-year postdoctoral fellowship launched by RWJF in 1983. Its purpose is to increase the number of faculty from minority and other historically disadvantaged backgrounds who achieve senior rank in academic medicine and dentistry. A commitment to eliminating health disparities is among the selection criteria.
The program supports one of RWJF’s major objectives: To increase diversification of the medical and dental professions and, as a consequence, improve the health care received by the nation’s underserved populations. Of Amos program scholars, RWJF senior program officer David M. Krol, MD, MPH, says, “Ultimately, we would like to see these individuals from historically disadvantaged backgrounds becoming full professors at prestigious institutions, putting out important, valuable work, looking at a variety of different issues—including how to decrease the disparities between rich and poor, majority and minority—while climbing the academic ladder.”
Keith Black has certainly fulfilled the program’s purpose.
1Black K. Brain Surgeon. New York: Wellness Central, 2009.
Keith Black uses surgery/research to seek cure for glioblastoma multiforme - the most malignant brain tumor