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Explaining the Biology Behind Bioterrorism

By Brian Loux

ASSOCIATE NEWS EDITOR

Recent threats and rumors of bioterrorism on American institutions have set many members of the public and the media on edge. Still, even with all the focus, most are left with burning questions about the “mysterious white powder” people have found on envelopes, and what scientists are doing about it.

After the events of the past week, it may appear that even our own college campus is susceptible to such an attack. But scientists are saying that even the worst case scenarios may not be all that menacing. Still, the readiness of the nation to respond to such an attack remains in question.

What is anthrax?

The powders of anthrax, known in the scientific community as Bacillus Anthracis, behaves very much like any other bacterial contagen. “Anthrax is a disease of intoxication, where the organism is inhaled, ingested, or is inserted under the skin,” said Michael N. Starnbach, an Associate Professor of Microbiology and Molecular Genetics at Harvard Medical School. “It enters the body as dormant spores, and then germinates into bacteria and begins replicating once inside the body.”

The bacterium secretes three distinct proteins, which cooperate to kill the host organism and aid in replication. The first protein is classified as “Protective Antigen,” or PA. Though not harmful in itself, PA binds to cellular membranes to serve as the delivery molecule for the other two deadly proteins, known as “Lethal Factor” (LF) and “Edema Factor” (EF). Once able to enter the cell via PA, LF will disrupt cellular activity and result in cell death. In the meanwhile, EF is left to disrupt the the cell’s ion flow, resulting in an accumulation of fluid in between cells, known as edema. “The activity of these toxins is the majority of the disease itself,” said Starnbach.

Like many other bacterial diseases, there is a vaccine for anthrax which induces the creation of antibodies against the anthrax toxin. The vaccine is an injection of large amounts of PA, which the body then learns to treat as a foreign invader, developing the proper antibody against PA. These antibodies alter PA such that it will no longer be able to bind the cell membrane, subsequently blocking the path for the fatal proteins.

Vaccine readiness in question

An antibody sounds simple enough to create, right? After all, they’ve been made for everything from the common cold to Alzheimer’s Disease. Unfortunately, there are a limited number of anthrax vaccines in existence for many reasons. Foremost, “the demand has been quite low outside the military since now,” said David Schauer, an assistant professor of Bioengineering at MIT.

However, he said that vaccines can’t be produced by just any lab. “While they are gearing up production efforts now, there won’t be many groups able to produce a safe vaccine. There aren’t good systems to test the efficacy of the vaccine, which most likely would have to be done in animals and requires great safety.”

The vaccine is produced by only one company, called Bioport, which has not been able to produce the amount of vaccine for which they were contracted. Being the sole contractor since 1998, they had failed to meet Federal Drug Administration (FDA) standards twice in previous years due to poor documentation. While they have been spurred by the government, there has not yet been a date set for a third presentation to the FDA.

Smallpox also concern

Smallpox has been dubbed the second largest bioterror concern today. The Center for Disease Control signed a contract with Acambis in late September to recreate a 40 million dose stockpile of the smallpox vaccine. During the 1970s, organizations successfully “eradicated” the disease, though strains were left in laboratories around the world, which concerns many experts.

The United States had scheduled to destroy all of its remaining strains of smallpox in the near future, though that may change. Lyndsay Wright, spokeswoman for Acambis, said that the company has accelerated their program for vaccine production, but is not at liberty to explain the reasons used and methods employed for the accelerated program.

Large scale attack implausible

While anthrax has grown a reputation for being as the world’s worst threat since the atom bomb, scientists would argue otherwise. Anthrax is not contagious, which eliminates the possibility of secondary casualties. It also does not kill instantly, allowing the infected to be treated and saved. Also, development of an anthrax aerosol that could infect a large number of people has never been effective. “A much more technologically advanced terrorist group in Japan attempted to develop an anthrax aerosol and use it in a subway, but there were no fatalities,” Schauer said.

The inherent problems with effectiveness might make Anthrax a bad choice for a weapon. However, it is a terrorist favorite due to the ease with which it can be produced. “It’s quite easy to grow Bacillus Anthracis,” said Schauer. “Someone could probably grow it in their garage if they wanted, while growing a contagious strain like smallpox is a much more difficult task ... so there really is a catch-22 for bioterrorists.”

Over the past few weeks there have been speculations as to how many anthrax spores could kill a person, though there is no scientific evidence to back up any of these claims. “For obvious reasons,” said Starnbach, “there have been no tests on how anthrax affects humans, so these speculations are not based on any data.”

While there will always be a threat that a recombinant strain of a disease will be used as a weapon, Linda G. Griffith, an associate professor of Bioengineering at MIT, has worked with the Department of Defense to create a sensor network which could detect any form of biochemical agent. Griffith was unable to comment on the matter.

Modern day biological weapons have severe limitations, which comes as a great relief to all. “The only substantial thing that [biological agents] will be able to do is unnecessarily scare the populace,” said Schauer.

Anthrax’s uses

To some scientists, anthrax is not seen as just a threat, but instead may be a tool. Specifically Starnbach, in conjunction with his colleague R. John Collier at Harvard Medical School, has furthered the science of immunology with their research on anthrax’s method of transmission. “We are interested in using anthrax as delivery system because of the uniqueness with which PA can deliver components inside the cell,” said Starnbach. “The challenge [in medicine] is not to get the vaccine protein into the body but getting it into the cell so it can stimulate Memory T cells which can be activated upon actual exposure to the disease.” Some scientists have experimented with other methods to ensure that the proteins enter the cell, but have come across high safety risks. Collier and Starnbach, however, have combined proteins from anthrax with proteins from other viruses and bacteria against which they wish to immunize.

The PA protein guarantees that these proteins will enter the cytoplasm and induce memory T cells to create antibodies. “We do not work with the anthrax bacteria itself ... we are working with fragments of DNA housed in E. Coli,” said Starnbach, discussing the procedure’s safety. The team has already produced results with a vaccine against Listeria Monocytogenes, a bacteria that causes meningitis. They are also attempting to develop an HIV vaccine with the same method. This vaccine delivery technique is licensed by Avant Immunotherapeutics, who are working with Harvard Medical to develop the technology commercially.