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September 4, 2002 A better bug sniffer By Jeffrey Krasner US Genomics, a Woburn start-up with a novel machine that may one day read genetic information directly from DNA molecules, is working on a government project to create a front-line defense in the country's fight against bioterrorism.
The company plans to complete the $500,000 phase one research project by the end of the year. While the experimental work is far from an actual pathogen alert system, the program gives US Genomics funding to perfect its refrigerator-sized device in several crucial technological areas as it works toward a planned commercial introduction next year. It could also give US Genomics additional visibility as it seeks to transform itself from a privately funded start-up to a major supplier of equipment and data services for an anticipated boom in genomic research. While the future in the field of pathogen detection appears promising for US Genomics, the reality is more complex and fraught with greater uncertainty. To begin with, the company faces intense competition from potential rivals in the race for a machine that will rapidly detect deadly biological agents. And then there is the sheer complexity of the technology necessary to produce such a machine. ''We have an epidemic of companies coming forward with some type of rapid detection test for biological agents in the environment,'' said Michael Osterholm, director of the Center for Infectious Disease Research & Policy at the University of Minnesota. ''I've seen nothing out there that will provide us with a breakthrough. We need something that's going to fly, and so far we haven't gotten off the ground.'' The difficulty of building a better bug sniffer was driven home in July, when the White House Office of Science and Technology Policy said that devices deployed by the Post Office to detect anthrax didn't work and generate too many false alarms. The office ordered government agencies to stop ordering new anthrax-testing devices. The DARPA program is more complex yet. The agency wants to create a device that could detect any biological warfare agent, not a single microbe. To do so, a device would first have to isolate a specimen from the soup of microbes present in every breath of air, and then identify the bad ones. In support of his company's efforts, David Hoey, vice president of business development at US Genomics, said the company's GeneEngine's sensitivity makes it uniquely suited to distinguish between weapons of terror and common germs. ''The differences in the strains of anthrax that will kill you and the ones that do no harm are extremely minute,'' said Hoey. ''If there's something bad, you don't want to miss it - but you don't want to sound the alarm bell every time, either.'' US Genomics is at the forefront of a segment of the biotechnology industry that seeks to read and analyze genetic data at faster speeds and in ever-greater amounts. The company plans to use the DARPA funding to explore, in computer models, how the GeneEngine could be optimized to handle the needs of a military bug sniffer. If it is successful, US Genomics would create technolgies that go far beyond those used to map the human genome. The ''postgenomic'' era began in February 2001, when after years of high-profile, competitive research, a US government agency and a private company both published complete recipes of the human genome. The two groups claimed to have deciphered the exact sequence of chemicals that make up human DNA. DNA, the famous double helix, is made up of two intertwined spirals connected by pairs of chemicals - adenine, cytosine, guanine and thymine. Human DNA contains about 3 billion so-called base pairs. Sequencing the human genome was like reading the entire text of ''War and Peace'' while stopping to check the spelling of each word. Researchers split human DNA into millions of pieces, then used chemical reactions to identify the makeup of each base pair. At the end, computers were used to reassemble the decoded DNA fragments, in the correct order, into a single unbroken strand. US Genomics' approach is more like speed-reading the Cliffs Notes for ''War and Peace.'' Scientists use chemicals to identify a series of highlights along the DNA molecule, and then read those areas with a laser. The highlights yield a unique chemical signature, like a bar code, that can be used to instantly identify the type of DNA under study. ''The concept is you get a lot of very critical data by reading the right portions of the book,'' said Dr. Enrico Petrillo, a principal in CB Health Ventures, one of the early investors in the firm, who now sits on US Genomics' board of directors. ''You don't need to read every single word.'' The company was formed in 1997 around chief executive Eugene Chan's concept for an ultrafast DNA reader. So far, venture capitalists have invested about $25 million in the firm. Chan envisions a time when his GeneEngine becomes a key tool in a medical system where diagnosis and therapies are tailored to each patient's unique genetic makeup. Just as genetic mutations make some people more susceptible to certain types of cancer, a complete genetic code book could help predict what diseases are afflicting an individual, and how best to treat it. To put personalized medicine, as it is known, into practice will require a quick and cost-effective way to read each patient's genome. As the GeneEngine gets faster, Chan predicts it will become standard to include a ''smart card'' containing a genetic map in a patient's medical history. US Genomics' mapping method combines sophisticated biochemistry with the kind of basic technology found in a kitchen sink. Company scientists take a cell sample and extract DNA in a way that preserves long, intact strands of the molecule. Then, the DNA is ''tagged,'' or marked with chemicals known to bind to particular sites along the molecule. Suspended in water, the DNA strands are pumped into a tiny device, about the size of a computer chip. Inside the chip, the sample flows first through a microscopic grid of posts. Like a sink strainer, the posts trap the tangled DNA strand, until the flow of water carries it out, straightened, on the other end. Then, the strand zips through a narrow tube. Inside the tube, a laser is focused on the strand, making the chemical markers briefly glow. A computer records the markers, generating the bar code that can be compared against thousands in a database. The pattern of markers, like a grid, instantly identifies the source of the DNA. The whole process, operating at the molecular level, strains credulity - until you see a video the firm produced of DNA strands moving through the tiny processor. The DNA strands move through posts and the laser reader like so many pieces of spaghetti. US Genomics last month got a boost when J. Craig Venter, the president at Celera Genomics of Rockville, Md., who headed the industry effort to sequence the genome, joined its board. Venter, a media superstar who enjoys making headlines as much as knocking down scientific barriers, said he was convinced of the firm's technological promise during a visit to Woburn on Aug. 2. ''When you see the whole chromosomes flying, one at a time, through the
machine past the lasers - seeing is believing,'' he said. |