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Tiny particles just might save your life Researchers find ways to spy diseases no one else can see

Posted on: Wednesday, 10 December 2003, 06:00 CST

Six squares, each showing a line of six gray dots across the center, fill the flat-panel computer screen. It looks like a simple pattern for a tile floor.

For completely non-aesthetic reasons, the image pleases Jwa-Min Nam, Dimitra Georganopoulou and Savka Stoeva. They huddle around it, their faces so tight to the screen their shoulders brush.

"This is good," Nam says. "But we want it to be better."

The three young researchers at Northwestern University have taught atoms to sniff out a disease and bark like hound dogs when they find it. Today they're trying to isolate the "scent" of Alzheimer's disease.

But they're not there yet.

"There," as it applies to their current project, is the first- ever surefire diagnosis of Alzheimer's in a living person.

Eventually, their simple goal: To be able diagnose every disease ever known from a drop of blood - in a matter of minutes.

After a flurry of highly technical remarks laced with their respective native accents - Nam's Korean, Dimitra's Greek, and Savka's Bulgarian - the group disperses.

Savka hustles out of the narrow office that faces the lab at the Evanston campus. She dons a pair of goggles and begins the next experiment.

Other suburban researchers are using similar techniques with the equally immoderate goal of curing diseases in a matter of hours. Researchers at Argonne National Laboratory and the University of Chicago last week announced they have a method they hope will allow anyone ravaged by a biological weapons attack to cure themselves in a few hours - without stepping foot in a hospital.

'Brand new science'

Both teams fall under the dynamic field known as nanotechnology, the science of manipulating things molecule by molecule, atom by atom, in a world 10,000 times smaller than the width of a human hair.

The field promises to make the world better, faster and cheaper, and work like that by Northwestern's Institute for Nanotechnology is among the first to bring a whiff of medical applications to the market.

This week, nanoscientists and investors from around the country are converging on Chicago for a convention of what's becoming a big time for the world of the really small. Advances are coming fast, and many in the field are predicting a revolution with more pop than the silicon chip.

They credit a momentum that has reached "critical mass" in the last few years as several fields - materials science, molecular biology, physics and computer manufacturing - have converged on the once-impenetrable barrier of making things atom by atom. Suddenly the field of nanoscience, first envisioned by scientist Richard Feynman in 1959, is a reality.

Chad Mirkin, who leads the Northwestern nanoscience lab, says nothing will be the same after scientists plumb the atomic world, where, for example, gold atoms are actually red and clumps of silver atoms change from yellow spheres to greenish prisms for yet- unknown reasons.

"Everything, regardless of what it is, when you miniaturize it below 100 nanometers, it has new properties," Mirkin says, noting a single nanometer is one billionth of a meter. "It's a brand new science."

He and his team see immensely practical applications in that science. After finding, for instance, that a dab of sulfur on the outside of a sphere of gold atoms acts like Velcro for strands of DNA, they set their sights on one - using gold to diagnose diseases.

From atoms, hounds

Currently, there is only one way to be medically certain someone has - or had - Alzheimer's: an autopsy. The disease's chemical identification - call it a "scent" - is too faint to detect without clumsily rummaging through the brain itself, work that cannot be done on a live subject.

What was needed was a way to sniff out the chemical ID without ravaging the patient.

It was under that backdrop that the Northwestern scientists struck gold - or rather, took gold atoms and bred what amounts to a pack of extremely small, stealthy medical hound dogs they want to put on the trail of Alzheimer's.

If it works - or, in their minds, when it works - their new diagnosis will be cheap and ridiculously simple. It could be done in a doctor's office in a matter of minutes from a drop of blood or spinal fluid.

All the doctor would need is a handheld device that contains the "hounds" and can "hear" their distinctive howls that say they're found the scent.

None of the Northwestern team doubts they'll succeed.

They've already done it with prostate cancer, recently publishing their results in the journal Science. The method is 100,000 times more sensitive than any other technique, making it possible to diagnose the cancer before it sets in.

On this day, the order of business is singling out a protein unique to Alzheimer's. Once they find one, they'll use it to create a scent. Then they'll set their unimaginably tiny dogs after it.

Flushers and barkers

The hunt really involves two types of hound -"flushers" and "barkers," they might be called.

Both are nanoparticles - very small groups of atoms - affixed with a chemical that makes them stick to the telltale disease protein when they bump into it.

The magnetic flushers drive the disease proteins out of the thicket of cells and proteins in human blood where a magnet can find them and pull them into the open.

Once isolated - if they're present at all - the disease proteins are still too small to be seen. Enter Mirkin's barkers. They're gold particles, Velcro'd against thousands of strands of special DNA, which is much larger and more visible than any of the particles themselves.

They, too, are made to stick to the disease protein, and when another chemical is added, they release the DNA in a virtual explosion of gray dots. In essence, the hounds bark like mad.

So, if the doctor sees the dots, the disease is present.

After Alzheimer's, the Northwestern team will move on to the next pathogen. Could be breast cancer, could be anthrax. Could be anything. Eventually, they hope, it will be everything.

Mirkin envisions a day when different DNA is used to distinguish different diseases. Like a grocery-store scanner, his handheld device would tell what type of DNA is being released and therefore what diseases are present. Mirkin refers to this as "bio barcode DNA."

Personal stakes

Back in the lab, Georganopoulou jokes, "We're going to make doctors obsolete."

But for her, the prostate cancer research was no laughing matter.

"When I first joined this ... I thought it was a slight twist of fate," she says later.

Her uncle in Chicago, she explains, was in the late stages of the disease, the second-leading cause of cancer death among American men.

"All I kept thinking was how things might have turned out for him had he undergone early on some of the tests we try to develop here. Later on, when he passed away, I was determined to dedicate the first results of my research to him," she says.

The quip about doctors resonates with Shad Thaxton. As a pre-med student, he's the only member of the team likely to find himself using the products spawned from the lab.

"This stuff actually may be practical a few years down the road," says the Colorado native.

The group is taking a break outside the lab, which generally looks no different from an upscale high school's chem lab.

Brimming with confidence, the relatively young researchers under Mirkin muse about the implications of what they're doing. Amid talk of curing diseases and redesigning household products atom by atom, conversation turns to the Nobel prize. No one is too modest to say that possibility is out of the question for work like theirs.

But the Nobel isn't where they're immediately headed.

Nam is headed to a computer to take another gander at simple grids with gray dots. The others head back into the lab.

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