From the Lab to the World
by Carolyn Shea
The secrets of tuberculosis persistence. A new approach to treating cancer. The reasons why certain populations are precluded from getting the health care they need.
These are some of the weighty issues Evergreen alumni are investigating at laboratories and medical schools around the world. Their goal: improving human health and wellbeing.
One of these alumni, John McKinney ’87, directs the bacteriology lab at the Global Health Institute of the Ecole Polytechnique Fédérale de Lausanne (EPFL) in Switzerland. A microbiologist, McKinney has made important strides in understanding Mycobacterium tuberculosis, the intractable microbe that causes tuberculosis (TB). One of his discoveries, which exposed the key role a particular enzyme plays in the resilience of M. tuberculosis, has been hailed as a breakthrough in TB research. His lab focuses on studying the mechanisms that allow tenacious, infectious-disease-causing bacteria like the tuberculosis bacillus to persist in the human body in the face of immunity and therapy.
McKinney got his start in the field while working on an independent project in Betty Kutter’s bacteriophage lab at Evergreen. “That was when the research bug bit me and I knew I was hooked,” he says. He went on to earn his Ph.D. at New York’s Rockefeller University and completed postdoctoral studies at the Albert Einstein College of Medicine before returning to Rockefeller to direct its Laboratory of Infection Biology. While there, he says, “It became clear to me that in order to tackle the most interesting and important problems, we would have to adopt an engineering approach. In 2007, I moved to the Swiss EPFL, an engineering school, in order to establish a new interdisciplinary program at the interface of two very different fields—microbiology and microengineering.” This program employs high-tech tools, such as time-lapse microscopy, to fathom bacterial cell behavior.
McKinney considers his decision to concentrate on an underserved area of public health—infectious disease in general and tuberculosis in particular—a likely outcome of being immersed in Evergreen’s “philosophy of public responsibility, good citizenship and global justice.” He says, “Many citizens of rich countries like the U.S. think that diseases like tuberculosis have been conquered. Nothing could be further from the truth! On a global scale, tuberculosis kills more people now than ever before. But more than 99 percent of those deaths—which number about 2 million every year—occur in poor countries.”
“My dearest hope,” says McKinney, “would be to put myself out of work by making a discovery that would eliminate tuberculosis as a serious threat to global public health. Alas, I do not think that there is any chance that tuberculosis will be eliminated in my lifetime. Second best would be to make a discovery that had a significant impact on the quality of life for the world’s poorest people, for example a new therapy for curing drug-resistant tuberculosis or reducing the time that it takes to treat the disease. There I think we do have a chance of succeeding.”
James Chen ’76, a board-certified neurosurgeon, is tackling the problem of cancer. Chen studied marine biology at Evergreen and earned a master’s degree in exercise physiology and his M.D. from the University of Washington. After completing his residency at the University of Michigan Hospitals, he returned to Washington, where he served as the attending neurosurgeon at two community hospitals in King County and operated his own practice for more than eight years. “From there, I became interested in research,” he says. “It was self funded, started in my garage, where I had set up a lab. I was looking at the effects of photoactive drugs—drugs activated by light—on antibiotic resistant bacteria.” Chen used light-emitting diodes (LEDs) to stimulate the drugs to kill the bacteria. “It worked!” says Chen. “That led to the cancer research that I do now. I just started investigating it in the context of looking for new therapies that could be utilized in the patients I was treating.” These included people with malignant brain tumors and spine tumors, he says.
James Chen, chief scientist of the Bellevue-based biopharmaceutical company Light Sciences Oncology, holds his cancer-fighting LED device. Inserted into a tumor, this light-emitting instrument activates a photosensitive drug aimed at destroying the malignancy. Chen's firm recently won two therapeutic discovery grants from the federal government for its work. Totaling nearly a half-million dollars, the grants acknowledge Light Sciences' "significant potential to produce new therapies...and advance the goal of curing cancer within the next 30 years."
In 1995, he co-founded the Bellevue-based biotech company, Light Sciences Oncology, which is developing drugs activated by LEDs that can zap cancer cells without affecting healthy cells, too. The LEDs are inserted through the skin using a biopsy-like needle that goes directly into a tumor, attacking it from the inside out, rather than outside in, the method used in many standard treatments. Chen’s light-activated treatment, which also closes tumor blood vessels that supply cancer cells with oxygen and nutrients, is meant to fight the malignancy without damaging the healthy tissue nearby. Evidence was presented at last year’s annual meeting of the American Society of Clinical Oncology that the drug-light combination might have the secondary benefit of rousing the immune system to fight cancer cells in other parts of the body as well.
Chen’s firm, which employs more than 30 people and has a former director of the National Cancer Institute chairing its scientific advisory board, is targeting a number of cancers, such as colorectal cancer—the second leading cancer killer in the United States—and liver cancer, the third leading cause of death from cancer worldwide. It has completed Phase 3 clinical trials for treating both these diseases—the last stage of testing before getting regulatory approval from the FDA. The company has other applications for its lightactivated therapies in the pipeline, too, including ones for benign prostatic hyperplasia (enlarged prostate) and other non-cancerous conditions.
But it is cancer that Chen, Light Sciences’ chief scientist, is squarely aimed at. “I view cancer as the disease that causes the most suffering, not just because of the disease itself, but also because the current therapies have so many side effects. We have completely inadequate weapons to combat it. I look forward to continuing what we’re now doing— developing more effective therapies with fewer side effects for patients.”
combat cancer. I look forward to developing
more effective therapies with fewer side effects
— Neurosurgeon James Chen
Sandi Pruitt ’98 was interested in two things when she went to Evergreen: “I wanted to become a midwife and I was interested in studying health issues across different cultures.” She entertained the notion of going to medical school and concentrated her liberal arts studies on women’s health issues. Eventually, because of her work with a local Planned Parenthood office, she says, “I was introduced to the concept of public health and the needs of populations as a whole.”
After working in South Carolina as a maternal and child health educator, she realized she was more interested in working with populations than individuals. She discarded the ideas of becoming a midwife and a physician and enrolled in graduate school at the University of Texas Houston Health Science Center's School of Public Health. There, she analyzed—and published journal articles about—such concerns as media coverage of emergency contraception; geographic disparities in the prevalence of adolescent girls being vaccinated against human papillomavirus (HPV), the primary cause of cervical cancer; and the number of abandoned and surrendered newborns in Texas over a 10-year period. Her dissertation probed the relationship between socioeconomic status and cancer screening, a topic to which she would later return. In 2008, Pruitt received her doctorate in behavioral science and health promotion.
Last July, Pruitt completed her postdoctoral fellowship at the Washington University School of Medicine’s Division of Health Behavior Research in St. Louis, Mo., and then joined the school’s faculty as a research instructor of medicine. Her current investigations are concentrated on expanding her earlier HPV work and continuing to study geographic, socioeconomic, and racial disparities in cancer. She recently received a three-year career development award to document geographic disparities in late-stage colorectal cancer across the United States and to determine the role other factors, such as diagnostic delays, play in those disparities. “Although I’m very much in a research-oriented environment,” says Pruitt, “I don’t sit at a bench in a lab. I primarily do statistics, cleaning, gathering, analyzing and using data, forming hypotheses and writing a lot.”
— Researcher Sandi Pruitt
Pruitt says Evergreen’s emphasis on social justice, which gave her the ability to explore issues of inequality, “is critical to what I do everyday. There are rampant disparities in health care in the U.S. One of my main motivations comes from a social justice perspective. I’m doing my little part to identify and clarify what the inequalities are so that we can move towards doing something about them.”
Photo of Sandi Pruitt courtesy of Washington University School of Medicine in St Louis.