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http://www.wired.com/wired/archive/10.09/gvaccines.html Take These Genes and Call Me in the Morning By Amanda Griscom In a concrete bunker at Fort Detrick Army Base in Frederick, Maryland, Jenny Riemenschneider is standing over 10 rabbits splayed out on stainless steel operating tables. Dressed in a white Tyvek jumpsuit, a surgical mask, a shower cap, and plastic booties, she calmly loads 12 gold bullets into a revolver. Each rabbit lies motionless, tranquilized, paws spread-eagle with an exposed patch of shaved skin on its lower abdomen. Riemenschneider grips the pistol with both hands and presses its 8-inch barrel into a pink belly. Boof! Boof! Boof! Boof! Boof! Boof! Boof! Boof! She fires eight shots into the first rabbit, flinching slightly as the blasts echo through the room. A smile rises from behind her mask. "Looks good," she says. "See those clouds — those faint blushes just beneath the skin? Those are the bullets. It's a perfectly painless procedure." Riemenschneider is part of a team of military scientists experimenting with so-called gene vaccines as a weapon against the growing threat of bioterror. Her revolver? A medical device known as a gene gun, which fires capsules containing thousands of DNA-coated gold pellets designed to inoculate the bunnies against anthrax. Propelled into the rabbit's skin cells by a blast of compressed helium, the DNA fragments are supposed to train the animal's immune system to recognize and combat the actual disease. Six months later, when Riemenschneider exposes the rabbits to what should be a deadly dose of anthrax, she's ready to declare success: Nine out of 10 remain healthy. Gene vaccines may be relatively new, but they're the logical outgrowth of two familiar strands of medical science. First is the 200-year-old practice of vaccination, in which the body is infected with a weakened form of a disease that prepares the immune system for a future encounter with the real thing. Traditional vaccines are highly effective at conferring long-term immunity against diseases like measles, mumps, and polio, but because they involve growing and injecting a live pathogen, they're costly, cumbersome to produce and transport, and too dangerous to use against super-virulent viruses like HIV. What's more, traditional vaccines are effective only against infectious diseases — afflictions like cancer and Alzheimer's are left to more radical treatments, such as chemotherapy and surgery. While immunologists grappled with such limitations in the 1970s, an explosion of knowledge in the field of genetics led to a new approach to tackling disease: gene therapy. Gene therapy aims to conquer genetic diseases by replacing targeted genes. The concept was promising, but the medical record has been unsuccessful because the body's immune system rejects therapeutic DNA as foreign — just as it would reject a common bug. Gene vaccines borrow from both traditional vaccinology and gene therapy. By isolating a harmless snippet of a pathogen's DNA and injecting it into the body, researchers believe they can fool the immune system into developing an attack plan against a particular disease even though the body was never exposed to it. Whereas gene therapy tries to work in spite of the immune system, gene vaccines harness the immune system's instinct to search out and destroy alien proteins. "I still can't believe it actually works," says Riemenschneider, who has spent seven years investigating killer viruses such as Ebola. "DNA vaccines are incredibly easy to make. You can produce them in days or weeks, whereas the traditional methods often take years." Gene vaccines hold special promise as weapons against diseases too complex or dangerous for traditional immunology. Already, they've proven successful in hundreds of animal trials against bioweapons like anthrax and the plague, as well as against pandemics like malaria and TB, which claim millions of lives each year. In July, Oxford scientist Adrian Hill began testing a gene-based malaria vaccine on hundreds of at-risk people in Gambia. Closer to home, a gene vaccine against melanoma has completed three rounds of clinical trials on humans and appears ready to be submitted to the FDA for final approval. When injected directly into cancerous tumors, the vaccine, called Allovectin-7, causes proteins to grow on the tumor's surface — which in turn stimulates the immune system. The drug's manufacturer, Vical, is reviewing data from the experiments in hopes of presenting them to the FDA. If the drug gets a thumbs-up, Allovectin-7 may be on the market as soon as next year — and may unleash a torrent of new research. "When the flagship product makes it through the process, it will be a landmark proof of principle," says Vijay Samant, Vical's president. "Investment dollars will pour into both the vaccine and gene therapy industries." The same principle that allows gene vaccines to destroy melanoma is being applied to diseases once thought resistant to immunization. In April, Merck announced that its gene-based HIV vaccine had induced immunity in more than half of the 300 human subjects in its ongoing phase 1 trial. These results, by far the most successful yet for an AIDS vaccine, astonished the medical community. "This is without question the most promising technology that has come along for an AIDS vaccine," says Jeffrey Laurence, senior scientific consultant at the American Foundation for AIDS Research, "but keep in mind that we still have a long, long way to go to find a cure." The distinction between inducing immunity and preventing infection is critical: While the Merck vaccine successfully bolstered immune response — significantly slowing the infection process and reducing the likelihood of full-blown AIDS — it did not prevent infection altogether. Any gene-based HIV vaccine will require years of research before it can officially be proven effective and brought to market. Meantime, there are vaccines in the pipeline for bacterial diseases like anthrax, viral pathogens like Ebola, and inheritable diseases, including several forms of cancer and Alzheimer's. An Alzheimer's vaccine, for example, would stimulate the immune system to attack the protein deposits in the brain that are caused by the degenerative disorder. The same principle could be applied to all sorts of health issues. There's even talk of gene vaccines being used to prevent pregnancy (by training the immune system to attack the cells that produce sperm) and to conquer drug addiction (by blocking the brain's receptivity to the drug). But why stop there? "There's evidence that the elimination of a particular glucose response element in the cell makes mice live longer. We could selectively eliminate that receptor by immunization," says Stephen Albert Johnston, director of the Center for Biomedical Inventions at the University of Texas Southwestern Medical Center and a leader in gene vaccine research. "This technology has transformed our understanding of what a vaccine can do. Not just to prevent disease, but to probe the complex strategies of the immune system so we can use them to our advantage." <A HREF="http://www.ctrl.org/">www.ctrl.org</A> DECLARATION & DISCLAIMER ========== CTRL is a discussion & informational exchange list. Proselytizing propagandic screeds are unwelcomed. 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