X-Message-Number: 18763 Subject: SF Gate: Searching for a supervaccine/Scientists turn to primitive side of human immune system to develop a single drug to battle an array of biological weapons From: "Peter Christiansen" <> Date: Mon, 11 Mar 2002 08:59 -0800 ---------------------------------------------------------------------- This article was sent to you by someone who found it on SF Gate. The original article can be found on SFGate.com here: http://www.sfgate.com/cgi-bin/article.cgi?file=/c/a/2002/03/11/MN159545.DTL ---------------------------------------------------------------------- Monday, March 11, 2002 (SF Chronicle) Searching for a supervaccine/Scientists turn to primitive side of human immune system to develop a single drug to battle an array of biological weapons Leslie R. Guttman, Chronicle Staff Writer Spurred by the threat of bioterrorism, a small group of scientists is focused on inventing "universal drugs" they say would work more efficiently than vaccines -- by stimulating the immune system to fight off a wide range of threats. The players make up an unusual cast, from a former Cold War enemy to America's foremost expert on holistic medicine. They say there are so many biological threats a terrorist could make use of -- from anthrax, smallpox and plague to botulism, Ebola and tularemia -- that it would be impossible to vaccinate the entire U.S. population for each one. Instead, scientists say, the answer lies in creating what are being called broad-spectrum or universal drugs to boost the body's "innate" immune system enough to fight a range of pathogens. The approach is a departure from the medical norm of using drugs and vaccines meant to treat specific diseases. "Clearly, there's a role for this in terms of increasing general resistance -- not just for treating bioterror agents, but for infectious diseases," says Dr. Peter Rosen, an expert on emergency medicine in San Diego. Rosen headed an Institute of Medicine panel in the late '90s on improving civilian response to chemical and biological terrorism. The panel of 20 experts decided that research into innate immunity "was an area of biology that should be encouraged," Rosen said. The human immune system is really two systems -- the innate and the adaptive. For years, researchers have concentrated on the sophisticated workings of the adaptive system, which includes antibody-producing and other cells that have an extraordinary ability to recognize and selectively attack invading microbes. Increasingly, however, scientists are focusing on the innate system, a primitive class of cells that is the body's first line of defense, kicking into action within minutes of detecting an invader. The skin belongs to this system, as well as cells called macrophages, which gobble and kill pathogens, and "natural killer" cells, which poison them. One scientist promoting the broad-spectrum approach is Ken Alibek, former deputy chief of the Soviet Union's secret biological weapons program. Alibek's small biotech company outside Washington, D.C., is working on using proteins called cytokines to boost innate immunity. A POISONOUS CLOUD Alibek says a likely bioterror scenario is a poisonous aerosol cloud blown over a city. In his drugs, he says, cytokines act as messengers to activate macrophages and natural killer cells in the respiratory tract at the beginning of exposure -- "creating a window of opportunity to prolong life span until you get specialized medical care." He foresees people stocking his company's nasal sprays and pills in their home first-aid kits and says the drugs would work for a long list of threats, from smallpox to hemorrhagic fevers. Alibek also believes that if the concentrations inhaled were low enough, the drugs could eliminate pathogens by themselves. Ironically, Alibek has received funding from DARPA (the Defense Advanced Research Projects Agency, created in 1958 during the Cold War to fight the very enemy Alibek once was before his defection about 10 years ago. His firm, Advanced Biosystems, has received $12 million from DARPA and other federal agencies. Alibek expects it will take two to five years to get his products to market, depending on future financing. The Defense Advanced Research Projects Agency is well known for its willingness to bet money on risky projects such as the military computer network that ultimately morphed into the Internet. MEDICINAL MUSHROOMS Another proponent of the innate immune system approach is Dr. Andrew Weil, the Harvard-educated M.D. and best-selling author on alternative medicine. Weil is talking with the agency about testing medical mushrooms as immune system enhancers. "DARPA is very interested," Weil said. "Mushrooms are nontoxic, they're cheap and they can be produced in large quantities to make pharmaceuticals." As Weil explains it, the polysaccharides, or large sugar molecules contained in the mushrooms, appear to act as Paul Reveres for the immune system, alerting it to danger. "One theory is that they resemble components of bacterial cell walls, so the immune system recognizes them as a class of substances it needs to act against and revs up," Weil said. He adds that medicinal mushrooms have been used for centuries in Asia. Weil's plan calls for $500,000 in financing, which is small change in the world of clinical trials, but with it, he says, "we could accomplish an enormous amount of work." But the approach has plenty of skeptics. One of them is Stanford University bioterror expert Steven Block, who said there is "no evidence" medicinal mushrooms could cure diseases like inhalational anthrax. "These are serious diseases, and they're going to require serious medicines, " he said. "Maybe there will be some compounds in the mushrooms (to create drugs)," but obtaining "a real scientific understanding will be a long haul." TRICKY RESEARCH Of Alibek's work, Block says cytokines are "very potent modulators of the immune system" that require caution in drug research because they aren't fully understood. To illustrate his point, Block recounts how an experiment conducted last year by Australian scientists had alarming results. While trying to make a mouse contraceptive, the scientists tinkered with the mousepox virus, a relation to human smallpox, and accidentally increased the virus' killing powers. The researchers were trying to increase production of the cytokine interleukin-4, on the theory that a highly sensitive immune system would attack and reject a mouse egg. But the genetic tinkering instead increased the infectiousness of the virus, and many of the mice injected with the would-be birth control died. But other scientists are undeterred in the research into enhancing immunity. Roger Loria, a scientist at the Medical College of Virginia, is testing the effectiveness of steroids as an immunity-boosting defense against the threat of nuclear radiation or a "dirty bomb." Loria is working with androstenes, a class of steroid in the body that breaks down into the sex hormones estrogen and testosterone as well as into immune-regulating hormones, which is where Loria's focus lies. In experiments, he says, 70 percent of the mice exposed to radiation levels above the dosage that rained down on Hiroshima, were protected when the steroids increased the body's ability to produce infection-fighting cells and blood-clotting factors depleted by the radiation. Hollis-Eden Pharmaceuticals of San Diego has acquired rights from Loria and other scientists to develop such drugs. The company has spent $50 million so far on research and just signed a partnership with the Department of Defense for an undisclosed amount to work toward FDA approval for military and civilian use of the drugs. Alibek remembers when the road toward legitimacy was rockier. "Five years ago, when I talked to government officials (about innate immunity), they said, 'Ken, you'll never get funding.' Now, many people -- scientists, colleagues and government entities -- are supporting it." The former Cold Warrior, who speaks in the rolling cadence of his native Kazakstan, added, "Whenever I start thinking everything's going too slow, I remember: Five years ago, I knew two letters of the English alphabet." E-mail Leslie Guttman at ---------------------------------------------------------------------- Copyright 2002 SF Chronicle Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=18763