Friday, July 11, 2008

A Narrow, narrow miss

kw: book reviews, nonfiction, viruses, biology

The Colonels Jaax, Nancy and Jerry. In 1983, Nancy Jaax came within a few microns (the thickness of a surgical glove) of being infected with Ebola Zaire, the "hottest" strain of Ebola virus. It was her second time working in a BSL 4 containment, in a "blue suit", and her first experience doing any work there.

BSL 4, BioSafety Level 4, describes a total isolation (as near total as is technically possible) between specimens containing infectious viruses or bacteria, and those who work with them. This very costly sort of "clean room" (or very, very dirty room, if you think of it) containment for specimens, including living (temporarily) lab animals such as infected monkeys, is reserved for a handful of the most dangerous agents, including several strains of Ebola and the Marburg virus.

These two relates species make up the genus of the filoviruses, or thread viruses. They and other BSL 4-rated species kill 10% or more of their victims, typically within a week or two of exposure. By contrast, the much-feared AIDS virus, HIV, though it seems to kill at least half, takes one or two decades to do so.

Have you ever had surgery, with the antiseptic washes, the surgeons and nurses in scrubs, masked and gloved? If so, you were in a BSL 2 containment, and it was you who were being protected. It costs tens of thousands of dollars (or Euros) to set up BSL 2 facilities, and tens of millions for BSL 3 or 4.

This is the Marburg Virus. Ebola looks about the same. It takes an expert to distinguish the various thread viruses from photographs. Biochemical and DNA tests are needed to be sure which strain and which species is which.

In a way, these are very primitive viruses. The thread is a protein structure about 70nm in diameter, or about 1/20th the diameter of an E. coli bacterium. The structure is hollow, containing a simple coil of RNA and another protein or two that initiate RNA transcription and duplication once the virus is taken into a cell.

Cells can be remarkably stupid. They tend to take anything into themselves that is coated with protein. Many viruses take advantage of this.

Once a cell contains an active ("living" is not really the right word) virus particle, it changes completely. Enzymes in the cell help the virus remove its protein coat, and others get suborned by the RNA and replicase proteins. The cell begins to make copies of the virus's RNA. The raw RNA is a (-) strand. Copies from this strand are (+) strands. The (+) strands and the cell's ribosomes begin making virus proteins (there are fewer than ten for a filovirus).

Once some (+) strands have been made, the replicase proteins will, by chance, produce equal numbers of (+) and (-) strands of RNA. The (-) strands and the virus proteins self-assemble into new virus particles (the uncoating enzymes have been deactivated by this point). The (+) strands keep churning out new proteins. In the case of Ebola and Marburg, the cell gradually fills with one or more "bricks" of compacted virus particles. When a brick contacts the cell wall, the cell ruptures, spilling out a few million viruses that infect all the cells in the vicinity.

The above sequence takes no more than a few hours. Because filoviruses travel through the blood stream, they invade the whole body in short order. Cells of every kind, in every imaginable location throughout the body, become filled with virus bricks, then burst, and so on. Within a few days, to at most two weeks, symptoms such as headache begin. Depending on which specific strain one has, there is a chance between 24% and 90% that the whole body will melt down and turn to a mixture of destroyed cells and viruses. This kind of explosive amplification can result in an ounce or more of each pound of body weight becoming virus. That is whole continents, whole planets, whole galaxies full of viruses, billions of billions of billions, taking over a body in just those few days.

It is not known what species is the reservoir for any strain or species of filovirus. One of the very few things we think we know: All known filoviruses are very, very deadly to primates, including humans.

The above is good background to prepare your mind for reading The Hot Zone by Richard Preston. Just nineteen years ago, around Thanksgiving time in 1989, there was an outbreak of a new strain of Ebola in a "monkey house" in Reston, Virginia. Reston is a suburb right outside the Washington, D.C. beltway. The monkey house in question housed 500 monkeys from the Philippines, that were being prepared to be sent to laboratories around the country. These 500 never made it out of the building...

The Hot Zone chronicles the Reston outbreak, sandwiching it between a clear, chilling introduction to Marburg and the two main strains of Ebola, and an account of the author's pilgrimage in 1993 to Kitum Cave, in Kenya. The Marburg virus is thought to originate near there, perhaps in one of the species endemic to the cave...but we don't know for sure.

The book lacks an index. It lacks little else. It has been called a bio-thriller, but it is much more than that. The language is not hyped in the way you'd expect of a fictional thriller. It is as matter-of-fact as butter on bread, but as compelling as a ride on a roller coaster. Early on, I looked up some of the principal players, such as the Jaaxes shown above, especially because I couldn't bear the thought that she might have died.

She lived, and lives today. She and her husband were central to the military operation that (with the company's permission) cordoned off the monkey house, made the whole place into a BSL 4 containment, and destroyed all life within it, first the monkeys and the viruses they contained, then every insect, bacterium, and virus within its walls. That is, everything was killed that the team was able to detect and verify as dead. One can never know for sure.

Strangely, the Reston strain of Ebola is not known to have caused any human deaths...yet. We can't say if we dodged a bullet, or if the bullets simply were a strain that kills monkeys but doesn't affect humans. We simply don't know if there are lots of other filoviruses out there that can't infect people. We only know of the six or seven that can.

Author Preston makes it clear that there is no way to ensure that this won't happen again. The tropics are a day away by modern aircraft. A person infected with Ebola has three to ten days of no symptoms, in which to travel to London, New York, Paris, Tokyo, New Delhi or Beijing...and at least the Reston strain and one other can be transmitted in the air, by a cough or perhaps just by speaking. At any time we could be less than a month away from the near-depopulation of planet Earth.

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