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Rewriting Life

Lab on a Swab

Researchers at the University of Michigan want testing for the influenza virus to be as easy as taking one’s temperature.

Imagine that a pandemic flu has broken out in Asia. An airplane carrying exposed passengers is traveling across the Pacific Ocean toward Los Angeles. One of them begins to cough, causing palpable fear to spread throughout the cabin.

Acting swiftly and efficiently, a flight attendant pulls a small device from the overhead compartment, takes a throat sample from the ailing passenger, and identifies the virus as the influenza. On landing, all the travelers are quarantined – and the spread of the flu is thwarted.

It’s a scenario that may become a reality in the not-too-distant future, thanks to a group of researchers who’ve been working on ways to derive genetic information from human DNA more efficiently.

Furthermore, if combined with a wireless network, it could track the spread of flu strains throughout the world.

It all began with a small device – and a big idea.

In 1992, a multidisciplinary group at the University of Michigan started developing a lab-on-a-chip device, called a Genotyper, as a way to reduce the steps needed to glean genetic information from human DNA using microfabrication methods. (See Notebook for the lab-on-a-chip concept.)

DNA-derived information can be used in testing everything from whether a chicken is safe to eat, to the origin of a blood stain at a crime scene, or if a child has the influenza virus.

After several years of prototyping, Michigan researchers began to discuss potential applications of the Genotyper device, which is about the size of a TV remote control.

“The advantages are that [the Genotyper] is very portable,” says Ronald G. Larson, chair of the chemical engineering department at Michigan. “It seemed ideal for doing on-the-spot genomics on viruses – and influenza was a logical candidate.”

So they began to build a device that can quickly identify the genetic makeup of the influenza virus.

Since influenza is an RNA virus, the RNA must be first converted to DNA before it can be amplified on the chip. In the process, called PCR (polymerase chain reaction), enzymes are released that digest, or cut, the DNA at certain points.

“The way the gene is cut or not cut depends on which flu gene you have,” says Larson. The DNA fragments are then run through a gel and stained with fluorescent tags, allowing scientists to distinguish one flu strain from another, or to tell if a new strain has emerged.

So far, the Genotyper has been tested on human genes, mice (a common source for searching out genetic variations), and on the DNA in two strains of influenza.

“You have a sort of microprocessor, or hardware piece,” says original group member Mark A. Burns, professor of chemical and biomedical engineering at the University of Michigan. “Then you just put on different software, but in our case you would call it wetware, different reagents, to do tests of different things.”

The Michigan researchers have not gone through the process with a throat sample because they need to solve the purification issue (see Notebook). Thus far, they’ve taken pre-purified DNA and genotyped it.

Although it’s been 36 years since the last worldwide influenza pandemic in the human population, the threat of a contemporary outbreak is always present. Recent outbreaks of avian influenza underline that reality. Furthermore, because of its genetic mutability, rapid transmission, and ability to move from animal to human, the need to track new variants of the flu virus is critical. According to William A. Petri Jr., professor of medicine, microbiology, and pathology at the University of Virginia, virtually all flu experts agree that another influenza pandemic will occur.

As a physician, Petri envisions a Genotyper-like device being used some day to quickly identify the type, subtype, or strain of the influenza virus in a patient, and then a doctor using the information to select the appropriate drug.

Petri notes that most patients today wait two to three days before visiting the doctor. If they were able to diagnose themselves at home within the critical 48-hour period, they could get more effective treatment – and decrease the chances of infecting others.

In 15 to 20 years, researchers hope that a patient can take a nasal swab or throat sample, put it on the Genotyper chip, and self-diagnose their condition at home. Then data could be entered into a wireless network and variants of the flu mapped neighborhood by neighborhood, city by city, or beyond.

Burns envisions a half-dozen other possible uses for such a genetic-detecting integrated device (see Notebook). But he also acknowledges that there’s the potential for the technology to be abused. Unscrupulous health insurers or potential employers, for instance, could intercept information about an individual’s genetic make-up and discriminate against policy-holders or employees. 

But how feasible is such a revolutionary diagnostic device?

“Getting something like this to really work at a commercial level involves many things, not only technologically, but also sociologically, economically,” says Larson. Despite these caveats, though, he thinks it could become mass produced and inexpensive.

“What we’re really trying to do is prod the field forward and focus on what we see as a big need for tracking viral pathogens,” Larson says. 

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