In Saliva Veritas

© 1998 Arnie RosnerHuman Saliva magnified 100×A trip to the doctor's office generally entails a deposit of blood or urine from which some diagnoses can be produced after a laborious process. Now, groups of biologists and engineers are working to make disease diagnoses quicker and more efficient by giving credit to a less conventional humor – the Rodney Dangerfield of bodily fluids – spit.In the past year and a half, the National Institutes of Health's National Institute of Dental and Craniofacial Research (NIDCR) has used a set of seven grants totaling $27 million (US) through 2006 to form a Salivary Diagnostics Group for technology development. Once disparate disciplines, oral salivary biology and engineering are melding in order to give saliva its due respect as a diagnostic fluid.Scientists and healthcare workers have long known the power of saliva to indicate HIV exposure or drug abuse. Indeed, certain informative molecules or analytes in saliva, such as DNA, RNA, peptides, or fatty acids, could indicate a variety of conditions including cancer, Alzheimer, and heart disease. "It turns out that almost anything you can measure in blood, you can measure in saliva," says NIDCR director Lawrence Tabak. But often, informative saliva analytes are present in hard-to-detect levels – one hundredth to one thousandth of what's found in blood. Qualitative measures are feasible, for example, when someone tests positive for HIV antibodies. But quantitative measures, such as a precise glucose level, are not.Nanoscale sensors may break down the barrier, says David Wong, chair of the Division of Oral Biology and Medicine at the University of California, Los Angeles. Such sensors could eventually detect "virtually anything that one wishes to detect at single-molecule level," says Wong.Wong and his engineer colleagues are designing nanosensors to detect trace analytes. In a recent paper, he and his group report the first comprehensive detection of mRNA in saliva.1 Wong uses oral cancer as a salivary diagnostic test case, and he is starting to look at breast cancer and diabetes.He envisions that within a few years, researchers will be using high-throughput nanosensors to test for 10 different ailments simultaneously. The tests would be quick, noninvasive, and could be done onsite in remote areas of the world, perhaps in cultures where blood collection is considered taboo.Other investigators are studying the feasibility of detecting salivary cancer analytes such as p53, or potential heart disease indicators such as C-reactive protein, a sign of inflammation.2University of Pennsylvania professor of biochemistry, Daniel Malamud, is working on a platform he hopes will improve HIV diagnosis by closing the so-called window, the highly infectious four to 12 weeks between infection and measurable antibody load. His group is seeking to reliably measure the virus according to multiple analyte signatures using a $3,000 toaster oven-sized detector that analyzes cassettes containing saliva samples. A single sample is separated into a series of channels: In one the instrument detects bacterial or viral antigens, and in another it detects human antibodies to the pathogen. From yet another channel the researcher can obtain the RNA or DNA fingerprint by PCR.The group is also seeking ways to detect the seven or so viruses and bacteria that cause all childhood respiratory diseases. By diagnosing these ailments within a half-hour rather than a few days, Malamud hopes to stem antibiotic overuse, a major cause of rampant antibiotic resistance. For now, Malamud's efforts are focused on one virus, HIV, and one bacterium, Bacillus cereus, a close relative of Bacillus anthracis.Salivary diagnostic approaches have many potential limitations, however. Before the FDA approves any product, scientists and engineers must account for practically every eventuality, for example, how recent meals or mouthwash use might affect test results. Furthermore, only some diseases present diagnostic biomarkers in saliva, and of those, only a portion may be reliably detectable.To discover reliable analytes, Wong suggests controlled studies in which researchers attempt to accurately distinguish known diseased individuals from normal individuals based on a suspected reliable analyte. Disease-specific bio-marker searches could be greatly enhanced with the planned completion of the "human salivary proteome," a research project for which NIDCR will soon award grants.Eugene Russo erusso@the-scientist.com is a freelance writer in Takoma Park, Md.

In Saliva Veritas

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