Posted on 10/17/2001 8:33:53 AM PDT by winna
3/18/98
Novavax Press Release: Novavax Microbicides Undergoing Testing at University of Michigan Against Biological Warfare Agents
9/27/98
University of Michigan News & Information Service: New Non-Toxic Compound Said to Destroy Anthrax Discovered
(This article is no longer online. It was previously available at http://www.umich.edu/~newsinfo/Releases/1998/Sep98/r092398a.html. The complete text of the article is pasted below)
SAN DIEGO---BCTP looks like skim milk. Laboratory rats gain weight when they eat it. Spray it on your lawn and the grass will thrive. But according to tests conducted by University of Michigan scientists, this seemingly benign material could be a potent weapon against anthrax---one of the deadliest bacteria on Earth.
In a presentation at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) on Sept. 26, Michael Hayes, research associate in the U-M Medical School, presented experimental evidence of BCTP's ability to destroy anthrax spores both in a culture dish and in mice exposed to anthrax through a skin incision. James R. Baker Jr., M.D., professor of internal medicine and director of the Center for Biologic Nanotechnology in the U-M Medical School, directed the research study.
BCTP was developed by D. Craig Wright, M.D., chief research scientist at Novavax, Inc.---a bio-pharmaceutical company in Columbia, Md.---and president of Novavax Biologics Division. According to Wright, the material is made of water, soybean oil, Triton X 100 detergent and the solvent tri-n-butyl phosphate.
"One of the most remarkable characteristics of this material is its ability to rapidly destroy a wide variety of dangerous bacteria and viruses, while remaining non-toxic to people, animals or the environment," Baker said.
BCTP's effectiveness against anthrax spores is especially significant, because they are so difficult to kill. "Spores are like freeze-dried bacteria," Baker explained. "Their tough outer coat is resistant to disinfectants, freezing, drought, virtually anything we can throw at them. Spores can survive in the environment for many years and still generate live bacteria when given the right combination of water, nutrients and temperature."
Concentrated doses of strong disinfectants like bleach or formaldehyde will kill anthrax spores, according to Baker. Unfortunately, they also are toxic to people and the environment, which makes them useless for decontaminating a person, a piece of land or equipment exposed to the bacteria.
Since the Persian Gulf War, military authorities have become increasingly concerned about the threat anthrax and other biological warfare agents pose both to our armed forces and civilian populations. "Anthrax is often fatal and easily dispersed through air or water," Baker said. "We know that countries hostile to the United States have developed strains of anthrax which are resistant to antibiotics and existing vaccines. To counter that threat, the Defense Advanced Research Projects Agency (DARPA), is testing several possible new weapons against these biologic agents---including BCTP."
"When properly formulated, the components in BCTP form an emulsion of tiny lipid droplets suspended in solvent," said Wright. "These lipids fuse with anthrax spores causing the spore to revert to its active bacterial state. During this process, which takes four to five hours, the spore's tough outer membrane changes allowing BCTP's solvent to strip away the exterior membrane. BCTP's detergent then degrades the spore's interior contents. In scanning electron microscope images, the spores appear to explode."
In his conference presentation, Hayes described how even low concentrations of BCTP killed more than 90 percent of virulent strains of Bacillus anthracis spores in a culture dish. "We observed sporicidal activity with dilutions as high as one part BCTP per 1,000 parts culture media," Hayes said.
To determine its toxicity to animals, U-M scientists fed large amounts of BCTP to laboratory rats and injected mice with the material subcutaneously. The animals gained weight, remained healthy and suffered no adverse effects.
To determine BCTP's effectiveness at treating animals exposed to anthrax spores, Baker's research team subcutaneously injected mice with Bacillus cereus---a closely related species of bacteria that can be safely handled in a university laboratory setting. Like B. anthracis, its lethal relative, B. cereus produces large, ulcerous areas of dead tissue if it penetrates the skin through a cut or injury. If untreated, these skin infections spread systemically, producing severe illness and death in 80 percent of the laboratory mice in the study.
"When we washed the animal's skin lesions with BCTP, the wounds began to heal," Baker said. Mice receiving BCTP either simultaneously with B. cereus spores or whose wounds were washed with BCTP an hour after exposure had a 95 percent reduction in lesion size. The death rate for mice receiving BCTP was only 20 percent.
"Rapid inactivation of anthrax bacteria and spores combined with low toxicity makes BCTP a promising candidate for use as a broad-spectrum, post-exposure decontamination agent," Baker said.
In future studies, Baker plans to evaluate BCTP's effectiveness against inhaled anthrax spores, as well as other bacteria and enveloped viruses. His research has been funded by DARPA's Unconventional Pathogen Countermeasures Program. The U-M and Novavax have filed a patent application covering BCTP's use as a decontamination agent for various anti-microbial applications. Baker is a member of the Novavax scientific advisory board, but has no significant financial interest in the company.
Contact: Sally Pobojewski Phone: (734) 647-1844 E-mail: pobo@umich.edu
EDITORS: A black-and-white scanning electron microscope image of anthrax spores before and after treatment with BCTP is available on request. An announcement describing BCTP and the material's anti-microbial properties is being released simultaneously today by Novavax, Inc. _________________
NOTE: In accordance with Title 17 U.S.C. section 107, this material is distributed without profit or payment to those who have expressed a prior interest in receiving this information for non-profit research and educational purposes only. For more information go to: http://www.law.cornell.edu/uscode/17/107.shtml -----------------------
11/3/98
Medicalpost.com: Chemical kills anthrax, not harmful to animals
Researchers have found a chemical that is nontoxic to animals yet can kill spores of deadly toxins such as anthrax. Known by the acronym BCTP (bi-component Triton tri-n-butyl phosphate), the chemical inactivated more than 90% of Bacillus anthracis spores after four hours of incubation in vitro, and was also sporicidal against three other Bacillus species, said Dr. Michael Hayes (PhD), a research associate at the University of Michigan medical school. "Electron microscopy revealed an apparent disruption of spore ultrastructure after BCTP treatment," he told the recent Interscience Conference on Antimicrobial Agents and Chemotherapy here. BCTP looks like skim milk and consists of water, soybean oil, Triton X 100 detergent and the solvent tri-n-butyl phosphate.
University of Michigan Highlights of 1998
U-M scientists tested a new anti-microbial agent called BCTP and found it to be a quick and efficient killer of influenza A virus in cell cultures and in the nasal passages of laboratory mice. BCTP also could be a potent weapon against anthrax. James R. Baker Jr., professor of internal medicine and director of the research study, said that BCTP has a remarkable ability to rapidly destroy dangerous bacteria and viruses while remaining non-toxic to people, animals and the environment.
March 1999
Doctors for Disaster Preparedness Newsletter
A BETTER WAY ON THE HORIZON?From a report posted by Dorothy Preslar ( www.healthnet.org/programs/promed-hma/9810/msg00011.html ): A material developed by D. Craig Wright of Novavax, Inc., may be able to rapidly destroy a wide variety of dangerous bacteria and viruses, including anthrax spores. The material, called BCTP, is made from water, soybean oil, Triton X 100 detergent, and the solvent tri-n-butyl phosphate.Laboratory mice and rats thrive when fed the material."Rapid inactivation of anthrax bacteria and spores combined with low toxicity makes BCTP a promising candidate for use as a broad-spectrum, post-exposure decontamination agent," Baker said.(Such ProMED-mail postings contain news from around the world on disease outbreaks. The web site is a project of the Federation of American Scientists, who generally appear to be advocates of the "global village" and disarmament, but whose web site ( www.fas.org ) contains many key defense reports; the text of some important legislation, such as the Missile Defense Act of 1995; and congressional testimony on global warming as by John Christy, Patrick Michaels, Robert Balling, and Richard Lindzen.)
5/24/99
Dallas Morning News: Biological defenses still being planned
Researchers at the University of Michigan, for example, are testing a liquid designed to destroy bacteria and viruses but not people.For people, anyway, "this is probably less toxic than salad dressing," said Dr. James Baker, a researcher at Michigan.The liquid, called BCTP, contains water, soybean oil, a detergent called Triton-X 100 and a solvent called tri-n-butyl phosphate. When mixed together properly, these chemicals form microscopic droplets. Because they are smaller than bacteria and viruses, the droplets tend to fuse with the outer membrane of a microbe, destroying it in the process. The chemical mixture is harmless to people, Dr. Baker said.So far, the Michigan scientists, along with researchers at Novavax Inc. of Columbia, Md., have shown that the liquid can destroy spores of Bacillus anthracis, the bacterium that causes anthrax. Preliminary tests have also shown that the liquid, when sprayed into the nasal passages of mice, can decrease the number of spores that get into the animals' lungs.Dr. Baker said the liquid will be tested soon in military-run drills to see how well it performs outside the laboratory.
1999
University of Michigan: Anti-Infectives
This was written in 1999 but last updated on September 4, 2001. I assume if the information had been proven incorrect it would have been removed from the site!
This is a valuable result, since unlike other sporicidal agents, BCTP or BCTP 401 did not demonstrate any toxic effects. Other tests, conducted by the Center, showed that these emulsions are non-toxic if administered intramuscularly, intranasally, or orally. This lack of toxicity provides other potential sites for treatment. BCTP and its derivative BCTP 401 appear to have great potential as environmental decontamination agents or for treatment of casualties in either a military biological weapon attack, or a terrorist attack. The inactivation of a broad range of pathogens, including vegetative bacteria, enveloped viruses, and bacterial spores, combined with low toxicity, seem to make it suitable for use as a general decontamination agent that can be used even before a specific pathogen is identified. The nanoemulsions can be rapidly produced in large quantities and are stable for many months at room temperature. (Freezing causes separation of the oil and water phases.) Undiluted, they have the texture of a semi-solid cream and can be applied topically by hand. Mixed with water to dilute, they have a consistency and appearance similar to skim milk, and can be sprayed to decontaminate surfaces. The spray can potentially interact with aerosolized spores before inhalation. These properties provide a flexibility that will be useful for a broad range of decontamination applications.
1/19/00
RealAudio link: radio news story about DARPA’s Biological Warfare Defense program (aired on January 19, 2000)
University of Michigan: Non-Toxic Emulsion Foils Deadly Anthrax; Flu Virus Succumbs, Too (Adobe Acrobat .PDF, <1MB, 1 page)8/24/00
DARPA: Biological Warfare Defense (text)
9. DARPA has a small, but growing effort in decontamination. One of our first projects in this area involves “Novasomes” developed at the University of Michigan. Novasomes are a nanomolecular formulation of lipid and detergent. The formulations are nontoxic to us, but rapidly kill a wide range of gram positive bacteria and envelope viruses. The results here show killing of anthrax spores.
8/28/00
DARPA: DSO BWD 1 (Adobe Acrobat .PDF, 1.37MB)
text of page 9:Title: Nanomolecular Countermeasures(chart shows comparison of 1% bleach, 10% bleach, and BCTP 1:1000 in Anthrax spore kill)
Novasomes™ have significant bactericidal effect (> 99% killed) on gram positive bacteria and spores
Novasomes™ can be used to decontaminate vehicles and sensitive equipment
Novasomes™ are non-toxic to humans, plants, and animals
Recent Information:Anthrax Decontamination Letter by James R. Baker, Jr., M.D., Director Center for Biological Nanotechnology, University of Michigan Medical School
Since the discovery of anthrax in Palm Beach County, this web site has received many messages asking the U-M to "release its protective agent against anthrax." Here are the facts: In 1998, scientists at the U-M Center for Biologic Nanotechnology conducted research on nanoemulsions. In these experiments, the substance destroyed anthrax spores on surfaces and in laboratory mice exposed to the bacteria through a skin incision. The "formula" for the substance is not the issue. This material is the result of a unique manufacturing process. Unless it is manufactured in a specific manner and unless appropriate quality controls are performed, the resulting mixture could be totally non-functional. Thus, providing this information would not be helpful and might actually lead to a false sense of security. A private company called NanoBio currently is managing this project (see www.nanobio.com ). They are trying to accelerate approval from the Environmental Protection Agency to use the material for decontamination and cleaning. While the initial studies with mice were encouraging, the substance has not been proven effective in people. Until clinical studies are conducted and approval from the Food and Drug Administration is obtained, no one can say whether the substance will prevent anthrax infection in people. NanoBio is applying for approval from the Food and Drug Administration to conduct clinical trials and hopes to begin these later this year. Up-to-date information on anthrax is available on the Center for Disease Control web site at: www.bt.cdc.gov/Agent/Anthrax/Anthrax.asp
James R. Baker Jr., M.D.
Ruth Dow Doan Professor of Biologic Nanotechnology,
Director Center for Biological Nanotechnology
University of Michigan Medical School
STATUS REPORT - BIO-ATTACK DEFENSE
Ann Arbor, Michigan, USA, 11 October 2001 - In light of concerns that have been raised about an attack with biological weapons against US civilians, NanoBio Corporation offers the following information and perspective.The defense from an attack with biological weapons has three broad aspects: 1) detection of the threat and agent, 2) prophylactic medications or vaccines, and 3) bio-decon materials. Research by NanoBio's CSO, Dr. James R. Baker, Jr., conducted at the University of Michigan School of Medicine (UoM) has concentrated on developing remedies for aspects 2 and 3.Concerning aspect 2, the research into a prophylactic medication, a human protective treatment, to protect people exposed to bio-attack pathogens (Anthrax, Ebola, etc.) has resulted in a "protective and immune system stimulant" applied topically to the skin as a cream and to the mucous membranes aa a nasal spray. This technology has shown significant potential to prevent infection with inhaled influenza virus using a mouse model. This research is funded through March 2002 by an agency of the Department of Defense (DoD) known as DARPA (Defense Advanced Research Programs Agency). Further testing is planned by the US Army Medical Command's Institute for Surgical Research pending additional funding from DARPA or DTRA (Defense Threat Reduction Agency).Concerning aspect 3, the UoM research by Dr. Baker also has developed a remarkable bio-decon material to remove weaponized pathogens from surfaces, buildings, cars, clothing, etc. This technology is available today through UoM spin-off, NanoBio Corporation. The bio-decon material technology invented is that of "antimicrobial nanoemulsions" and it can be applied to skin and the environment without harmful effects. The classes of microbes eradicated are virus (e.g., Ebola), bacteria (e.g., Botulism), spores (e.g., Anthrax), and fungi (e.g., Aspergillus). The nanoemulsions also can be formulated to kill only one or two classes of microbes, as necessary. A "broad-spectrum" nanoemulsion was tested on surfaces by the US Army (RestOps) in Dec 1999 for decontamination of Anthrax spore surrogates. It was tested again by RestOps in March 2001 as a chemical decontamination agent. All tests were successful. The fact that the nanoemulsion also functioned as a chemical decontamination material is an unexpected plus. Dr. Jane A. Alexander, acting DARPA Director, stated interest in this nanotechnology for purposes of bio-decon for the skin in her statement before the Senate Subcommittee on Emerging Threats and Capabilities on 5 June 2001.NanoBio is aware of the immediate security need for producing and stockpiling the bio-decon material and plans to license the specific technology to accomplish this. NanoBio has requested emergency funding from the U.S. government so that the deployment of both the human protective treatment medication and the bio-decon material can be accelerated.///
1. A method of inactivating a Gram positive bacteria comprising contacting said Gram positive bacteria with a bacteria-inactivating emulsion, such that said Gram positive bacteria is inactivated, wherein said bacteria-inactivating emulsion comprises an oil-in-water emulsion in the form of a discontinuous oil phase distributed in an aqueous phase with a surfactant stabilizer, said oil phase comprising an organic phosphate-based solvent and a carrier oil.10. The method of claim 1 wherein said gram positive bacteria is Bacillus anthracis.
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