Dennis Matthews
How Technology Is Helping Medicine
October / November 2004
Volume 2 Number 5
Dennis Matthews didn't choose a career in health care technology so much as it chose him. Although his mother was a nurse, Matthews decided early in life to leave medicine to her and his older brother, who was studying to be a physician. Instead, he earned a Ph.D. in physics at the University of Texas in 1974, then went on to achieve an international reputation as a pioneer X-ray laser researcher at Lawrence Livermore National Laboratory.
But in the early 1990s, Matthews and his LLNL colleagues began to realize that their advanced laser technologies could be spun off to the private sector to benefit human health.
"Doctors were coming to us, saying they needed help from engineers and scientists to develop better tools for diagnosis, screening, and treatment," Matthews said. "Essentially, they were asking rocket scientists to develop medical devices.
"At first we said, are you kidding? We made no claim to know anything about medicine. But we do know the technology like no one else. So we told them, if you can define the problem well enough, we can make something that will work."
Matthews and Pat Fitch, then head of Livermore's Engineering Research Division, set up a multidisciplinary Center for Health Care Technologies and started hanging out with physicians and medical researchers.
"A doctor at UCSF (the University of California at San Francisco) invited Pat and me to see some surgeries," Matthews said. "We watched him take a gallbladder out of a pig with a minimally invasive procedure, and we were hooked."
One of the new center's first initiatives was to develop technologies to treat strokes. "Doctors, mainly neurologists and neurosurgeons, met with us," Matthews said. "There was no real treatment for stroke, they said—€”can you help us out?"
In 1995, Livermore invited doctors who treat stroke patients to meet LLNL's engineers, biologists, and physical scientists at a "Stroke Summit" at Wente Vineyards near the laboratory. The workshop led to a series of patented devices for diagnosing and treating stroke, and spawned several startup companies using Livermore technology.
In the midst of the 1990s technology boom, other Livermore inventions quickly became prime candidates for commercial development.
"We would invent something," Matthews said, "and a venture capital firm would turn it into a startup company. Or a development phase company, just getting up and running, which had run into a significant technical hurdle, would come to us and ask if we could help them out."
Some examples:
—€ Vysis, Inc., of Downers Grove, Ill., licensed LLNL's unique FISH (fluorescence in-situ hybridization) technique for detecting DNA abnormalities in chromosomes. The company, since acquired by Abbott Laboratories, is now marketing or developing FISH-based diagnostic kits for breast, bladder, blood and a number of other cancers.
—€ The laboratory's Peregrine system, an advanced method for targeting tumors with radiation treatment, is being distributed to a number of hospitals for testing and validation by NOMOS Radiation Oncology Division, of North American Scientific Inc., of Cranberry Township, Pa.
—€ Cepheid, a diagnostics instrumentation company in Sunnyvale, Calif., (please see related article, Page 23), licensed Livermore's "rapid PCR" (polymerase chain reaction) technique for analyzing DNA and has incorporated it into machines that enable physicians to perform real-time, point-of-care diagnostics from unprepared biological samples.
When the dotcom boom went bust and federal funding for medical technologies also tapered off, LLNL's Center for Health Care Technologies disbanded. Undaunted, Matthews established a Medical Technology Program involving several Livermore divisions and intensified the laboratory's collaborations with universities and medical research centers such as UCSF, State University of New York (Buffalo) and the Mayo Clinic.
Livermore's most extensive collaboration, however, has been with the University of California at Davis, located about 90 miles north of the laboratory near Sacramento.
"About five years ago," Matthews said, "the UC Davis Medical Center asked us for a meeting. Their physicians came down and told us what their favorite problems were.
"This was a great opportunity for us," he said. "They gave us lab space in the basement of their hospital, which gave us easier access to tissues for our research."
In 2000, Livermore teamed with the UC Davis Cancer Center to take on cancer, the nation's second leading killer. LLNL's staff of biologists, toxicologists, physicists and engineers joined forces with the cancer center's experts in patient-centered and clinical research, providing a clinical testing ground for Livermore's medical technologies. Matthews, who became the cancer center's associate director of biomedical technology, said the collaboration was a key factor in the center's being named a National Cancer Institute-designated cancer center in 2001.
"Cancer biologists have become my heroes," Matthews said. "They know what cancer cells look like and what they do and how they got there.
"It (the collaboration) was a concentrated effort in many areas, including devices and diagnostics. We focused on new concepts, such as the staging of disease, using protein arrays to diagnose biomarkers that would indicate a cancer or precancerous condition, and imaging tissue using optical signatures."
The collaboration also bolstered LLNL's efforts to commercialize its medical technologies. Livermore and UC Davis launched a "laboratory bench-to-bedside" Industrial Partners Consortium aimed at establishing partnerships that would develop prototype medical devices into commercial products, shepherd them through the approval process, and distribute them to the medical profession.
Well aware of the many potential uses of light and radiant energy, or photonics, in biological and medical research, Matthews applied for a National Science Foundation grant to establish a Center for Biophotonics Science and Technology at UC Davis. The $40-million, ten-year grant was approved in 2002, and laser expert Matthews, already holding down jobs at both Livermore and UC Davis, was named director of the new center—€”the only NSF center focused on biophotonics.
"Our task is to apply photonics concepts and technologies to biology and medicine," Matthews said—€”for example, using optical techniques to speed drug discovery by as much as a hundredfold. The two UC Davis centers will also work together to integrate cancer and biophotonics research.
Among their joint projects is the development of cellular-level precision surgery, which uses hyperspectral (narrow bandwidth) imaging to identify individual cancer cells and uses precision robotics and short-pulse lasers to destroy them one cell at a time. The technique could eliminate the need for chemotherapy and radiation therapy to destroy "outlying" cancer cells that might be missed by traditional surgery—€”a possibility Matthews calls the "Holy Grail" of cancer therapy.
Matthews said the same technique might also be used to treat epilepsy—€”by removing the epileptogenic centers in the brain that trigger seizures—€”and ease the effects of spinal cord injuries by excising bony tissue impinging on nerves, one micron at a time.
Livermore and UC Davis are looking for commercial partners to help develop a tabletop proton accelerator for proton radiotherapy, an improved cystoscope for detecting bladder cancer based on the optical signature of cancer cells, and a number of other medical and health-care technologies.
Since the 9/11 terrorist attacks, the two institutions have increasingly focused on technologies to improve homeland security. Both stationary and handheld systems to detect the presence of pathogens that might be released by terrorists, such as anthrax and smallpox, have been developed.
Another joint project is what Matthews calls "the emergency room of the future."
"We need to provide some help for emergency room docs," Matthews said. "In the (1995) sarin gas attack in Japan, physicians and nurses were harmed as well as those initially exposed in the subway. We need faster triage, point-of-care diagnostics, to determine if patients are acutely infectious or contaminated with radioactivity or toxic chemicals.
"A deliberately spread pathogenic or toxic agent might contaminate a whole hospital," he said. "We would then need a better way to handle the people seeking care. We may need to create trailers or sophisticated holding quarters that are physically disconnected from the hospital. We may even need to use robotics to treat them.
"LLNL can provide pathogen detectors and infectious disease monitoring systems to figure out what's wrong with you and deal with you accordingly."
Reflecting on his "second career" as a medical technology developer, Matthews said, "I remember visiting the hospital at SUNY Buffalo, where I saw a woman who had an aneurysm in a cerebral artery. The doctors were trying to get a catheter in to deploy a coil to isolate the aneurysm, but they couldn't —€”the cerebral arterial system has so many branches —€” and the woman died.
"I realized that I knew how to build some technology to get that catheter in there," he said. "It was an —€˜aha moment' for me."
Charles Osolin is a public information officer at the Lawrence Livermore National Laboratory.
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