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  Physician with a vision has his eye on a chip

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March 2006
Feature Story

Karen Titus

Given that it’s now easy to fly coast to coast in the space of an afternoon, it tugs at the imagination a bit to recall that earlier travelers took months to cover the same distance.

Michel G. Bergeron, MD, is hoping for a similar leap with point-of-care microbiology tests. One day, says Dr. Bergeron—a microbiologist and infectious disease specialist—physicians will marvel that it took days, sometimes weeks, for test results to become available. As they turn to rapid, DNA-based diagnostics, they’ll shake their heads and wonder, "What took us so long?"

Dr. Bergeron has big dreams, though some might say he’s merely a big dreamer. His vision is taking shape in a new organization he’s created, Diagnostics for Life. Read one way, it’s a positive message that captures Dr. Bergeron’s global view of diagnostics and its starring role in health care. Of course, taken another way, it could be a life sentence. But if Dr. Bergeron’s past successes with rapid tests are any indication, chances are good that his group could transform the practice of microbiology to "a culture without culture," as he likes to put it.

Dr. Bergeron, professor and chairman of the Division of Microbiology and of the Infectious Diseases Research Centre of Université Laval, Quebec City, was the primary force in developing two rapid microbiology tests, one for MRSA screening ("Border Patrol: MRSA Admission Screening," CAP TODAY, October 2005) and one for group B streptococcus (Bergeron MG, et al. N Engl J Med. 2000;343:175-179). He founded Infectio Diagnostic Inc., or IDI, which later merged with GeneOhm Sciences and was recently purchased by Becton, Dickinson, and Co.

Now Dr. Bergeron hopes to transform the microbiology laboratory from the outside in. Diagnostics for Life is an international consortium for developing point-of-care devices, drawing on the expertise of researchers from nearly every discipline imaginable. In his worldview, psychologists, economists, sociologists, and materials engineers have as much to say about diagnostics as do laboratorians and clinicians. If laboratorians are sometimes accused of walling themselves off from their colleagues, Dr. Bergeron has flung the doors wide open, turning the lab into a high-stakes open house.

So far, at least, the response has been good. At the group’s first meeting, held in Quebec City late last year, 38 researchers attended; overall, the group has nearly 100 members from 11 countries, Dr. Bergeron reports. "People were very enthusiastic. It’s early, and we’re building the group. But people are passionate about this vision."

The vision springs from the fertile mind of Dr. Bergeron, who recalls the dawning realization, some 10 years into his clinical practice, that he and his colleagues were—and still are—practicing empirical medicine, a slow process at best. Clinicians can make a diagnosis of pneumonia based on a physical examination and on a patient’s coughing and sputum expectorations but are unable to quickly pinpoint the bacteria, virus, or other microbe responsible. Sending a culture to the laboratory provides an answer—but only after two to three days or, with agents like tuberculosis, weeks.

"The microbiology that we are doing today is the microbiology of Pasteur," Dr. Bergeron says. "That’s the bottom line." Yes, tests have evolved considerably since Pasteur’s day, but "most of what we do still relies on culture."

It’s not cost-efficient, he notes. The sickest patients receive treatment with broad-spectrum antibiotics. While effective for microbes such as Klebsielleae and pneumococci, clinicians tend to maintain these expensive drug regimens even if test results later suggest a cheaper and arguably safer antibiotic, like penicillin, will suffice. "People usually don’t change their initial prescription," Dr. Bergeron says. "I’m an infectious disease specialist, and sure I change, because it’s my duty. But I’m an expert in this area. I’m a professor at the university. But most clinicians don’t bother. And that’s the basis of all our practice—empiricism. And that’s what we’re doing today, in 2006."

Eventually, says Dr. Bergeron, he realized that such practice was like "chasing our tails," as antibiotics bred resistant bacteria in a never-ending cycle. That’s when he started shifting his research efforts from therapeutics to diagnostics.

Dr. Bergeron turned to DNA-based diagnostics because their speed appealed to him. His goal was a rapid test—one that could be turned around in less than one hour, giving clinicians microbiology results at the same time they learned the results of blood work and x-rays. "If you pass one hour, I think you’re in trouble."

Of course, a rapid test would require DNA extraction from samples—whether sputum, urine, stool, blood, vaginal—so that’s where Dr. Bergeron and his colleagues first directed the bulk of their efforts. There was nothing easy about it, he says, noting that microbes can be notoriously difficult to break open, depending on their shape. Anthrax spores, for example, are extremely hard to access; cocci are less difficult, but still more difficult than rods.

Ultimately, he and his colleagues developed a real-time PCR assay for group B streptococci, followed by the MRSA assay. At the same time, Dr. Bergeron launched IDI.

Now Dr. Bergeron and his colleagues are working on a new type of test, which is where Diagnostics for Life enters the picture.

Their current focus is on DNA chips that combine compact disc technology, microfluidics, nanotechnology, and a new detection method that moves away from PCR. "My strategy is to increase the detection signal, instead of increasing the quantity of target," he explains. Currently his lab is working on developing three CDs that will, in essence, serve as a laboratory on a chip. One CD will handle sample preparation, one amplification, and one detection. The sample prep and detection CDs are already working, Dr. Bergeron reports. The next step will be to integrate the three CDs into one, combining it with a DNA chip. Dr. Bergeron’s vision: "POC tests need to be done very rapidly, and should be simple to handle." They need to be inexpensive, yet match the sensitivity/specificity of lab-based tests, he says, and should be easily done after only a few minutes of training. "Like a CD," he says. "It doesn’t take much to learn how to make a music CD work."

Dr. Bergeron has long worked with collaborators from other disciplines, but Diagnostics for Life is a giant step forward. In addition to working with specialists in microfluidics, biomarkers, and biosensors, he’s adding researchers with expertise in psychology, sociology, economics, public health, epidemiology, environmental sciences, law, anthropology, sociology, industry, finance—essentially a Noah’s ark of health care.

Nothing less is needed, he says, to ensure the success of rapid POC microbiology tests. "I’ve realized, with the first two real-time PCR assays that we developed, that acceptance of these tests is not that good," he says. Changing the culture of practicing physicians, of the microbiology laboratory, and of the health care enterprise will come easier if the problem is tackled by many minds. The other reason for the multidisciplinary approach, he says, is the rapid pace of technological advance. "I wanted collaborators who could add to this consortium new technologies that we could use for different diagnostic tests."

Diagnostics for Life will have three research platforms. One group will include researchers from psychological, sociological, and economic disciplines, who will evaluate the need and market for, and acceptance of, POC tests.

The second group is the technology and device development group, which will design, create, model, and test new devices. Included in this group are bioinformaticians and experts in biological markers, ranging from nucleic acids, proteins, and peptides to monoclonal antibodies, polysaccharides, lipids, and metabolites. The group will also include experts in biosensors, who will explore optical, electrochemical, and electric transducers; molecular labeling; optics; laser science; surface functionization; microelectronics; microfluidics; nanomicroarrays; and polymer science.

The third group, the evaluation group, will include clinicians, laboratory professionals, and experts in microbiology, infectious disease, oncology, toxicology, epidemiology, and pharmacogenetics, to name a few.

The three platforms will be combined at what he calls a universal diagnostic interactive/integrative station, or UDIS, an infrastructure he plans to build at Universit√© Laval that will contain virtual and actual laboratories. Sophisticated telecommunications will be a key part of the center, as Diagnostics for Life is a global effort. The center will also serve as a training facility and sample collection center. "We’re going to develop a diagnostics research organization. There are CROs—clinical research organizations. But diagnostics research organizations don’t exist."

Not yet, anyway. But Dr. Bergeron plans to change that. "I believe that in the future we’ll have lots of DROs spring up. One objective of our group is to sensitize people to diagnostics."

Dr. Bergeron, in short, wants to do nothing less than bring in vitro diagnostics to the world’s attention, putting it front and center alongside therapeutics.

Rapid diagnostics will serve the developed and developing worlds, he notes. "Just imagine affordable point-of-care testing for malaria and tuberculosis—together they affect more than 1 billion people."

Convincing fellow microbiologists may be one of his biggest challenges. His first PCR test met with disbelief, he recalls. "A few days before publishing my article in the New England Journal, I was presenting my data at a meeting." The audience didn’t know about the impending publication, Dr. Bergeron says, because of a prepublication embargo. "People in the audience kept saying, ’You’ll never be able to do this,’" he recalls. "No one believed it."

At another meeting, a microbiologist told him rapid PCR tests would put microbiologists out of business. Dr. Bergeron, not surprisingly, disagrees with such predictions. Microbiologists will be needed to interpret results, even more so as more tests are done; at the same time, the rapid tests should free microbiologists to do other work that now falls by the wayside. "Two-thirds of labs in North America don’t do hospital infection control, because they don’t have time," he says.

Eventually, he hopes, they’ll all see the light—clinicians, microbiologists, clinical pathologists, and, as he puts it, "the entire medical establishment." It won’t be easy. Nor will it be easy for Diagnostics for Life to fulfill its mission. But in Dr. Bergeron’s view, the most important element is already in place—the vision. "Without it," he says, "nothing can follow."


Karen Titus is CAP TODAY contributing editor and co-managing editor.