BIOTERRORISM: $1billion effort yields no bioterror defenses

Bryan Bender : Globe Staff / January 17, 2011

WASHINGTON — The Pentagon is scaling back one of its largest efforts to develop treatments for troops and civilians infected in a germ warfare attack after a $1 billion, five-year program fell short of its primary goal.
 Even the heavy infusion of research cash and a unified effort by university labs and biotech companies from Boston to California were insufficient to break through limitations of genetic science, according to government officials and specialists in biological terrorism.
Instead, the Pentagon’s next $1 billion for the Transformational Medical Technologies program will focus on better ways to identify mutant versions of Ebola, Marburg, and other deadly viruses. Those are among the genetically modified agents that officials fear could be used by terrorists or rogue states against urban or military targets.
The continued flow of money, even with the shift in strategy, should help Massachusetts and other states retain jobs and research labs focused on this arena.
“There is tremendous potential for further development of a biodefense subcluster in the state,’’ said James D. Rooney, vice president of the Massachusetts High Technology Council.
Among Bay State firms that have received contracts under the germ warfare effort is Worcester-based Microbiotix. Representatives from Microbiotix did not respond to requests for comment.
The new strategy represents a return to the drawing board for an ambitious program conceived after the Sept. 11 terrorist strikes and subsequent mailing of anthrax to members of Congress and media organizations — events that helped US military planners realize that the nation lacked adequate defenses against bioterrorism.
Scientists initially set out to develop new medicines capable of attacking viruses that might be altered by terrorists to make them more deadly. But after more than 50 research projects by more than 100 contractors — including biotech firms, pharmaceutical companies, and universities, including several in the Boston area — only two experimental medicines have shown promise. And even those are far from being ready for limited clinical tests, according to project officials.
“They are trying to come up with new medical technologies that are more difficult to develop,’’ said Crystal Franco, a specialist at the Center for Biosecurity at the University of Pittsburgh Medical Center who specializes in biological defense policy. “They are really trying to push the envelope.
Another hurdle in the government’s effort: such treatments cannot be tested in human clinical trials, which are typically required for Food and Drug Administration approval, because it is unethical to expose people to deadly virus in such a study, requiring animals with similar traits as humans to serve as surrogates.
Alan S. Rudolph, director of science and technology at the Defense Threat Reduction Agency, said in an interview that the agency will now focus more attention on ways of identifying new pathogens. That research could lay the groundwork for further advances in the development of antidotes that could eventually win FDA approval.
The new focus of the program will be making a “cadre of investments that are able to take an unknown sample that may contain different agents, and be able to determine very quickly what is in there,’’ Rudolph said. “It is our intent to continue to grow this capability.’’
He added the ultimate goal will still be to someday develop therapeutic remedies that could treat someone infected with any number of deadly viruses — what the Pentagon called “one size fits all’’ or “one drug, many bugs.’’
In addition to Ebola and Marburg, some of the potential biological threats on the Pentagon’s target list are Lassa, Sabia, Machupo, and Junin, especially modified versions designed to cause more severe symptoms of hemorrhagic fever that are more resistant to traditional drugs.
The difficulty in developing medicines so far, however, demonstrates how much more research is needed, say biological warfare specialists.
It turns out it is easier to modify a germ or virus for an offensive threat than it is to develop an effective defense, they said.
“The offensive capabilities outrun the defensive capabilities as the march of biology continues,’’ said Richard J. Danzig, a former Navy secretary and noted expert on bioterrorism who sits on the Pentagon’s high-level Defense Policy Board.
“The theory behind [the program] was these same advances should empower the defenses,’’ he said. “I think that intuition is worth exploring and investing in, but it is easier to conceive than to execute.’’
Margaret Kosal, an assistant professor at Georgia Tech who worked on the program between 2006 and 2007, said “there is a fundamental need for basic science. The low-hanging fruit has all been picked.’’
One Pentagon contractor involved in the program who was not authorized to speak publicly put it more bluntly: “We’re years away from any reasonable FDA certification, let alone production.’’
Franco said the project’s hurdles also highlight the need for ongoing taxpayer-investment commitments from government, to encourage private-sector focus on such technologies that will generate little in sales, compared to, say, cholesterol and diabetes treatments.
“These are not going to be blockbuster drugs,’’ said Franco. “It is different when the government is your only market. There needs to be incentives for companies to participate, to take it on for the public good.’’
http://www.boston.com/news/nation/articles/2011/01/17/after_1b_spent_pentagon_shifts_strategy_on_bioterror_threats/?page=full

BIOTERRORISM: Scientists Investigate Potential Ebola Countermeasure

Jan. 21, 2011
Scientists with the University of Illinois at Chicago published a study this month on a class of tiny molecules that apparently adhere to the Ebola virus, seemingly preventing the potential bioterrorism agent from entering and infecting human cells
Previously examined materials "appear to exert their effects by altering the cells' response to the virus once it's entered the cell -- by which time it's too late," according to chemistry professor Duncan Wardrop, one author of the analysis published in the Journal of Medicinal Chemistry.
The scientists conducted their study of more than 230 compounds using a nonlethal virus with the protein coat of Ebola.
"We found that our lead compound also inhibits Marburg," Wardrop said, referring to another highly deadly agent suitable for an act of bioterrorism. "That was a nice surprise. There's growing evidence the two viruses have the same cell-entry mechanism, and our observations appear to point to this conclusion."
Animal trials would be necessary to further assess the effectiveness of the molecules.
The newly published study could shed new light on the means by which the Ebola and Marburg viruses penetrate human cells, possibly aiding "development of new antiviral agents," Wardrop added (University of Illinois at Chicago release, Jan. 19).
http://www.globalsecuritynewswire.org/gsn/nw_20110121_5351.php

BIOTERRORISM: U.S. Will Expand Biosecurity Work to Africa,

Nov. 23, 2010 Martin Matishak

WASHINGTON -- The U.S. Cooperative Threat Reduction initiative will work to secure deadly pathogens in Africa to prevent their use as tools of bioterrorism, a key Defense Department official said yesterday.

  U.S. Senator Richard Lugar (R-Ind.), shown in 2008, recently led a U.S. delegation to study biosecurity measures at laboratories in several African nations. The United States intends to focus on preventing terrorist acquisition of disease agents from Africa, a Pentagon official said yesterday (Vano Shlamov/Getty Images).

The Nunn-Lugar program has effectively safeguarded biological weapons facilities in the former Soviet Union but deadly disease materials, such as Ebola and anthrax, remain for the most part unprotected at research institutions in East Africa, Andrew Weber, assistant to the Defense secretary on nuclear, chemical and biological programs, said yesterday.
"I've been to a lot of the former bioweapons laboratories in the Soviet Union territory and if you look at the diseases that they weaponized, the pathogen samples originated in Africa," he said during a global health and security conference organized by the University of Pittsburgh's Center for Biosecurity.
"We don't want terrorist groups to do the same thing that the Soviet weapons program did," according to Weber, who earlier this month accompanied Senator Richard Lugar (R-Ind.), one of the CTR program's creators, on a tour of biological research facilities in Kenya, Burundi and Uganda designed to highlight the potential threat.
The region has experienced terrorist attacks in the past from al-Qaeda linked groups such as the Shabab, an Islamic extremist organization that claimed responsibility for recent suicide attacks in Uganda, he said.
"Terrorism in that part of the world is not a hypothetical situation," Weber told the audience.
Lawmakers in 2004 expanded the U.S. threat reduction effort's mandate to include securing weapons of mass destruction and related materials outside the Soviet bloc.
The program is on track to receive roughly $523 million in fiscal year 2011, once the annual spending bills are approved by both houses of Congress and sewn together in conference.
More than $209 million of the proposed funds would go toward biological threat reduction in the former Soviet Union. That works includes safeguarding pathogens, developing laboratories that conduct research on disease countermeasures and some border security operations.
The CTR program has not previously addressed biological risks in Africa, according to Lugar spokesman Mark Helmke. The effort would eventually install new physical security measures and train more medical personnel, he told Global Security Newswire today.
The effort is currently making preparations to begin work on the continent and the "stage is set to move quickly," a Defense Department spokesman said today by e-mail.
Weber said recently the program was likely to provide several million dollars to African states to improve security at laboratories that store dangerous pathogens. He added yesterday that "big thrust and focus" of the initiative's biological engagement work in Africa would be to improve biosafety and biosecurity at research institutions.
Biosafety is often defined as measures intended to prevent the release of infectious agents within a laboratory or the outside environment. Biosecurity involves active methods to avert biological terrorism or other disease breakouts.
During their visit to the Kenya Medical Research Institute, which maintains dangerous pathogens including anthrax and Ebola, in the capital city of Nairobi, the U.S. delegation noticed that several orange bags filled with biohazard waste "were just sort of sitting around" on the ground because the facility's small incinerator had "pretty limited capacity," according to Weber.
"While we were there a stray cat went into one of the bags, had lunch, and then hopped over the wall into the largest slum in Africa," he added. "That's just an example of why we need to focus a little bit more on biosafety."
Weber said that while there has been "tremendous progress" in standing up "administrative" and human health laboratories in the region, veterinary facilities have been largely neglected by the international donor community.
For example, the Uganda Virus Research Institute, which once housed Ebola and Marburg samples, lacked the resources to deal with anthrax outbreaks that killed hundreds of hippopotamuses in recent years.
"They just didn't have the diagnostic tools to deal with that very effectively, so we're trying to help them out" by providing them with modern equipment that could lead to quicker diagnoses, Weber said. "I think that's an important gap that the Nunn-Lugar program can help fill is this lack of attention to the animal health laboratories."
After his speech, the senior DOD official predicted that the threat reduction effort would have a long-term presence in Africa.
"I think it's going to be, just because of the nature of endemic disease, it's going to be absolutely a continuation of the long-term strategic partnership in the region," he told GSN.
The decision to expand the threat reduction program into Africa rather than other regions was based on several priorities, including: the prevalence of endemic disease, the presence of terrorist groups with intent to use biological agents; and the level of existing infrastructure and capacity and the impact the effort could have on improving that, according to Weber.
"Unfortunately, there's terrorism in East Africa, as well as the South Asia region. So yes, we need to work in both; we need to prioritize. A lot of what I described should be a global effort but we can't start everywhere at the same time," he told GSN.
He noted that the U.S. Centers for Disease Control and Prevention has been engaged in the region for decades, with offices in both Kenya and Uganda.
Weber also predicted the Cooperative Threat Reduction biological engagement work would eventually make up half of the program's budget, noting that the disease effort began with $2 million in the late 1990s and has grown to more than $200 million in the pending budget cycle.
http://www.globalsecuritynewswire.org/gsn/nw_20101123_8958.php

BIOTERRORISM: Ebola and Marburg

thomas maugh
Synthetic nucleotides injected into monkeys can block the replication of Ebola and Marburg viruses, suggesting it eventually may be possible to protect humans against these deadly bioterrorism agents, researchers said Sunday.The monkeys get very sick, but most of them survive. The agents, called morpholino oligomers, are the first drugs approved by the Food and Drug Administration to go into clinical trials against the viruses — although those trials will, at least initially, be conducted in primates, not humans.The results are "a potentially important proof of concept but still a long way from a product that can be used with confidence against human infections," said virologist Alan L. Schmaljohn of the University of Maryland School of Medicine, who was not involved in the research. Schmaljohn cautioned that the drugs were given within an hour after infection and that they could be much less effective later in the course of the disease or against a more aggressive strain of the viruses.Nonetheless, the experimental drugs represent the first ray of hope against two viruses that are extremely difficult to deal with in natural outbreaks and that keep bioterrorism experts awake at night worrying about their potential use by unprincipled attackers.Ebola and Marburg are both members of the filovirus family, long threads of RNA that infect humans and other primates, causing hemorrhagic fever and, almost inevitably, death. Although researchers have been working frantically to develop drugs to treat infections, none has yet reached the stage of clinical testing.The morpholino oligomers are a new class of drugs in a family of what is known as antisense nucleotides. Antisense nucleotides are designed to bind tightly to specific areas of viral messenger RNA, blocking replication. Such compounds already are being used to treat certain types of cancer and cytomegalovirus infections, and they are being tested against HIV. The morpholino oligomers, developed by AVI BioPharma of Washington, D.C., have specialized attachments that stabilize the nucleotides and make them more effective.The genesis for the studies came in February 2004 when a technician at the U.S. Army Medical Research Institute of Infectious Diseases in Ft. Detrick, Md., accidentally stuck her thumb while working on mice infected with the Ebola virus. She was quickly placed in what researchers there called the "slammer," a maximum-containment isolation unit.Coincidentally, Dr. Patrick Iversen from AVI had delivered a lecture on campus that day about the use of antisense molecules against viruses. He volunteered to design and synthesize molecules to treat the technician if the need arose. The technician was not infected, but the research led to the report Sunday in the journal Nature Medicine.Virologist Travis K. Warren of the Army research institute and his colleagues studied one compound, called AVI-6002, in rhesus monkeys infected with the Ebola virus. They found that 60% of the monkeys given a sufficient dose survived the infection, but all who received no drug died.Separately, they treated 13 cynomolgus monkeys infected with Marburg virus with a second compound, AVI-6003, directed against that virus. All 13 survived. Treating monkeys infected with Ebola with the drug for Marburg produced no results, and vice versa, indicating that the treatment was highly specific.Because clinical trials cannot be conducted ethically in humans, the FDA permits such drugs to be tested in primates, and the group will soon begin such tests. If they prove successful, the drugs will then be tried when outbreaks of infection occur in Africa.Warren said the approach could be used to treat a variety of other infectious diseases and inherited problems. "Any disorder that involves a genetic problem can potentially be treated," he said.
http://www.latimes.com/health/la-sci-ebola-marburg-20100823,0,89592.story

BIOTERRORISM: Beware of animal diseases in Bioterrorism

Written by Dr. Sam Sewagudde
Thursday, 01 July 2010 11:05
The suspected outbreak of anthrax in hippos in Western Uganda in the past weeks has yet again reminded us of some of the ignored facts about animal diseases. I overheard someone on the streets of Kampala inform a colleague ignorantly that anthrax was a disease of those who live with or stay near animals in the villages. This totally shocked me and I felt like going over to him and giving a lecture of a lifetime. I, however, restrained myself and just thought about how they didn’t know that the same disease could be brought right at their footsteps in their so-called city. They were possibly unaware of what we call bioterrorism.It is possible for unscrupulous people to use known lethal animal disease agents as weapons of mass destruction. This is known as bioterrorism. Anthrax is indeed one of the microorganisms that can be used as biological weapons of mass destruction. The other significant animal diseases in that group include; Botulism, Plague, Tularaemia, Ebola and Marburg diseases. These diseases are of great public health importance because:The host animals or carriers that are sources of infection often show little or no sign of disease at all.The disease agents have mechanisms of propagation that allow infection to move from one individual to another.Their effects result in high mortality rates and have the potential for a major impact on the public.They can cause public panic and social disruption.They require special action when they occur and also need public health preparedness in order to limit their progress.Anthrax is clearly documented as one of the diseases whose agents have been used in the past for bioterrorism. This can be alternatively spread through spraying in the air, mailed packages and release in the ventilation systems of public buildings.In the wake of the September 11th, attacks on the USA, some people were reported to have been exposed to anthrax in powder form that had been sent to them as mail in envelopes. This incident, a classic example of how an animal disease can find you in the comfort of your office, sparked off a major public health awareness campaign on bioterrorism that got many US citizens and others around the world to be alert about such diseases.As for Ugandans, even though we are far from the USA, and that we probably have far less enemies, we should not ignore the likelihood of such events happening.
http://www.observer.ug/index.php?option=com_content&view=article&id=9109:animal-health-beware-of-animal-diseases-in-bioterrorism&catid=58:health-living&Itemid=89