Saliva: An opening to disease detection


Public health laws ban it on sidewalks, and teething babies can't seem to turn it off. But medical science has fallen head-over-heels for spit.

Spit, spittle or saliva -- the watery, slippery liquid produced by glands tucked in our cheeks and under our tongues -- is chock-full of hormones, salts, proteins, bits of genetic code and other "bio-markers." Scientists say these things hold buckets of information about the state of our health.

And thanks to recent gains in technology, researchers are now devising more sensitive tests to detect all manner of diseases -- such as HIV, Alzheimer's disease, rheumatoid arthritis, osteoporosis and cancer -- all from samples of humble spit.

"[The] idea has been pretty much pervasive ... that saliva is something that's there, but we don't even like it very much," said Paul C. Denny, a professor of diagnostic sciences at the University of Southern California School of Dentistry. But "there's been a cadre of people, fairly small over the years, that's said this is fairly remarkable stuff."

Their time appears to have arrived.

Since 2002, the National Institute of Dental and Craniofacial Research (NIDCR), part of the National Institutes of Health, has provided $35 million to scientists and engineers at seven institutions to develop saliva-based diagnostic tests and devices. Up to $45 million more in research grants could become available through the same program in the next five years.

Some of the latest discoveries, and the promise of saliva-based diagnostics, will be discussed today in Washington at the annual meeting of the American Association for the Advancement of Science.

Spit's chief advantage over blood and urine tests or biopsies is convenience. People are less likely to avoid tests, try to fudge them, or fail to return for the results if all that's needed is a quick swab and a short wait for a printout.

"It's totally noninvasive," said David Wong, a researcher at the University of California Los Angeles School of Dentistry. "You don't have to take a cup to the bathroom, where people can adulterate a sample if they want to. You don't need to stick a needle in your vein."

The Rodney Dangerfield of bodily fluids, saliva does far more than moisten stamps, lubricate our mouths and launch the digestion of starches in our food.

It carries growth factors that stimulate the renewal of the cells that line our intestines. It washes our teeth and remineralizes them with calcium. Without it, our choppers would be dissolved by the things we eat and drink.

Sugars in our saliva produce the slippery, slimy coating that blocks infectious agents from invading the tissues of our mouths and causing sores that could threaten our health.

Saliva has anti-microbial factors such as immunoglobulin A that kill or neutralize viruses, bacteria and fungi, and enzymes that break down the dead invaders. And the flow of saliva from glands to gullet flushes them away.

Scientists have known for decades that saliva mirrors the blood, carrying much of what also flows in blood serum.

For couples trying to make babies (or avoid them), Wal-Mart and other retail stores sell the OvulationScope -- one of several lipstick-sized microscopes on the market that can reveal, from a spot of saliva, when salts are present that signal the onset of ovulation.

Some employers are also using saliva-based tests for illegal drugs, and they may win FDA approval for use in federally mandated drug tests, according to Edward J. Cone, a drug-testing consultant and president of ConeChem Research in Severna Park.

"It's growing in popularity," he said. "It's not necessarily designed to be a total substitute for urine testing, but it does the same thing."

Police agencies in Europe are already evaluating saliva tests as a tool to quickly screen impaired drivers for drug use, Cone said. Positive results from saliva tests would lead to more sophisticated lab tests. Unlike urine, which reflects recent drug exposure, saliva reflects real-time blood levels, and "tells you something about the actual state of the individual being tested," he added.

Scientists have long suspected that other constituents in saliva might help diagnose disease. But lab technology wasn't sensitive enough to detect them. "That technical hurdle has recently been overcome," Wong said. Engineers are developing micro-labs that can produce results in minutes.

Meanwhile, microbiologists looking for tests to diagnose diseases from saliva are mapping the human saliva "proteome" -- the identities and proportions of all proteins in the saliva of healthy people.

"Then you begin to look for diseases like diabetes, Alzheimer's and cancer, and ask whether people who have these diseases have unique protein changes in their saliva that could be used as a signature of that disease," Wong said.

It turns out that they do. In the December issue of the journal Clinical Cancer Research, members of Wong's team at UCLA reported they could detect "messenger" RNA in saliva -- genetic material matched to oral cancer proteins -- with 91 percent accuracy.

"The future journey for us and others is to determine the value of saliva diagnostics for high-impact diseases, such as diabetes, Alzheimer's, breast cancer, lung cancer and prostate cancer," Wong said.

His lab has already tackled some of those questions, and plans to report the first results later this year. "It's looking very encouraging," he said.

At the University of Mississippi, Dr. Roger B. Johnson, professor of periodontics, discovered that the saliva of sheep suffering from osteoporosis -- a weakening of the bones common in elderly people -- contained telltale compounds produced by reabsorption of bone by the body.

"Then we went to humans and saw that it was also elevated in women that had low bone mass," he said. His saliva tests can now diagnose osteoporosis with 95 percent accuracy.

Daniel Malamud, a biochemist at the University of Pennsylvania's School of Dental Medicine, has shown that he can detect both the HIV virus and a close relative of the anthrax bacterium in saliva. He is working with a Bethlehem, Pa., manufacturer of a saliva-based drug test machine to adapt the device to test for a variety of infectious agents.

"There's a cassette that moves the sample around through a series of channels," he said. Each channel leads to a "capture zone" that would fluoresce in the presence of certain nucleic acids, proteins or antibodies associated with infectious agents.

The cassette reader could transmit the diagnosis instantly from an ambulance to the hospital, Malamud said. In a doctor's office, the quick diagnosis could help avoid the precautionary use of antibiotics, a major factor in the evolution of drug-resistant diseases.

Paul Denny's lab at USC has discovered that the number of cavities we acquire by adulthood is tightly linked to the precise assortment of sugars that populate our saliva -- a genetically determined sugar profile that is also present in the blood.

He suspects that some of those sugars prevent cavity-causing bacteria from attaching to our teeth, while others facilitate attachment. "From a saliva sample, we can forecast the number of caries [cavities] in that person's mouth," he said.

The test is accurate to within one filling.

With that data, Denny hopes to develop a saliva test that can be performed in the dentist's office and predict how many cavities a child will develop by the age of 20.

The data can even predict which groups of teeth will be most susceptible to decay. With that information, Denny said, "the practitioner has a rationale for what teeth they should focus on for preventive measures" such as sealants.

In time, Denny believes, saliva tests may become central to how we monitor our health and spot developing problems.

"Somebody spits in a cup, dips a monitor in and out pops values for 10 different tests that say 'You're doing great,' " he said. "It's going to be a tremendous driving force, and the whole of medicine is going to be changing; and dentistry along with it."

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