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In the weeks following the September 11, 2001 terrorist attacks, there was a series of anthrax attacks in the U.S., resulting in five deaths.  The anthrax attacks triggered fear of other acts of bioterrorism, including the use of the smallpox virus.  According to the Centers for Disease Control (CDC), there is enough vaccine in storage to vaccinate everyone in the U.S. if there is an emergency.

However, according to one scientist, there's a potential problem.  He's sounding the alarm about the World Health Organization's (WHO) plan to genetically modify the smallpox virus for antiviral drug screening studies.

This is Dr. D.A. Henderson, who was the Director of the World Health Organization's global smallpox eradication campaign, from 1966-1977.



Quick facts about smallpox

The smallpox virus has been infecting exclusively human populations for thousands of years.  The last U.S. case of smallpox was in 1949, and the last case in the world was in 1977.  It spreads by direct contact, especially with bodily fluids.  It has a one to two week incubation period; the initial symptoms include a high fever, heachaches, body aches, and vomiting.  The disease is the most contagious with the appearance of the rash and subsequent pustules (warning: graphic photo!), which can spread into the mouth.  It has a 30% mortality rate; you can read more about it here.  Smallpox was so widespread in Southeast Asia that there was a smallpox goddess in India, know as Sitala.

Obviously, the smallpox eradication program worked very well; the only case since 1977 was a laboratory accident in 1978.  Following that accident, all stores of smallpox in the world were destroyed, except for those at the CDC in the United States, and the Vector State Research Center, in the Koltsovo, Novosibirsk region in Siberia.


D.A. Henderson sounds the alarm about genetically modified smallpox

In November 2004, the WHO approved genetic modification of the smallpox virus for screening of the effectiveness of new antiviral drugs and vaccines:

In 2003, US scientists asked the committee for permission to insert a "marker" gene into the virus, and to transplant its genes into other viruses in the same "orthopox" family. The committee had "significant reservations" about the work.

But at a November meeting it approved the research in principle. Each study must still be approved individually by the committee, as well as the relevant local biosafety authorities, says Geoffrey Smith of Imperial College London, who chaired the meeting.

In one kind of experiment scientists will insert the gene for a fluorescent protein from jellyfish into the Variola genome - so the live virus will light up, and the dead virus will not. This will allow large numbers of potential antiviral drugs to be screened rapidly for their ability to kill Variola.


Well, that sounds good in principle, but some scientists have expressed reservations:

Professor Donald Henderson, of the Centre for Biosecurity at the University of Pittsburgh, said he feared that tinkering with the genetic makeup of the variola virus - which causes smallpox - might accidentally produce a more lethal form of the disease.

"What I worry about is that there is rather too much done in this area and the minute you start fooling around with it in various ways, I think there is a danger," Professor Henderson said. "I'd be happier if we were not doing it and the simple reason is I just don't think it serves a purpose I can support. The less we do with the smallpox virus and the less we do in the way of manipulation at this point I think the better off we are."


He's basically saying that messing around with the smallpox virus genes, even if it's only to insert a gene to make the live virus glow, is risky.


He's not alone in his concerns.  Similar concerns were expressed in general in October 2001, and more specifically in October 2003:

A scientist funded by the US government has deliberately created an extremely deadly form of mousepox, a relative of the smallpox virus, through genetic engineering.

The new virus kills all mice even if they have been given antiviral drugs as well as a vaccine that would normally protect them.
The work has not stopped there. The cowpox virus, which infects a range of animals including humans, has been genetically altered in a similar way.

The new virus, which is about to be tested on animals, should be lethal only to mice, Mark Buller of the University of St Louis told New Scientist. He says his work is necessary to explore what bioterrorists might do.

But the research brings closer the prospect of pox viruses that cause only mild infections in humans being turned into diseases lethal even to people who have been vaccinated.

And vaccines are currently our main defence against smallpox and its relatives, such as the monkeypox that reached the US this year. Some researchers think the latest research is risky and unnecessary.
"I have great concern about doing this in a pox virus that can cross species," said Ian Ramshaw of the Australian National University in Canberra on being told of Buller's work.

Ramshaw was a member of the team that accidentally discovered how to make mousepox more deadly.  But the modified mousepox his team created was not as deadly as Buller's.


You can read Ramshaw's publication here, and Buller's publication here.  Those are the hardcore nerd journal articles.  Although the New Scientist article is rather sensationalistic, it is essentially accurate.


I feel that if you read between the lines of these articles, several things are apparent:

♦ 9/11 made everyone far more concerned about the remaining stores of smallpox, as well as potential dangers from genetic variants ("them evildoers is gonna get hold of the stuff!")

♦ A line must be drawn between useful experiments and unnecessary ones.  For instance, there have been some promising results with anti-smallpox drugs.

The question remains:  where do we draw the line, and how much do we have to worry about terrorists using bioweapons?  Are these just scare tactics?


Interesting reading

Level 4: Virus Hunters of the CDC.  Non-technical book by Dr. Joseph McCormick et al., about their detective work, tracking dangerous viruses in Africa and other places.

The Columbian Exchange: Biological and Cultural Consequences of 1492, by Alfred W. Crosby, Jr., about the role of smallpox in the Conquistadors' exploitation of Native Americans, as well as the effects on the New World ecosystem.

The Cobra Event by Richard Preston (author of The Hot Zone).  This is fiction, and it's pretty scary stuff, easily read in one night.  You won't sleep.


Cross-posted on Liberal Street Fighter.

Originally posted to Page van der Linden on Thu Jan 27, 2005 at 09:14 AM PST.

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