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Saturday, November 20, 2004 2:30 PM

plan would allow 20% of viral genome to be released to approved labs

 

 

http://www.biomedcentral.com/news/20041119/02/

 

November 19, 2004

 

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7 recommendations on smallpox

WHO committee plan would allow 20% of viral genome to be released to approved

labs | By John Dudley Miller

 

When the World Health Organization's (WHO) external advisory committee on

smallpox recommended last week that WHO allow the two research teams still

possessing the virus to insert a green fluorescent marker gene into it to test

the efficacy of potential anti-smallpox drugs, the committee also made at least

six other research recommendations, according to a WHO spokesman, including at

least two that some researchers find controversial.

 

The additional recommendations, which along with the green-marker proposal have

yet to be approved by WHO, would allow labs around the world to work with

fragments of the variola virus as large as 20% of the whole genome, according to

Daniel Lavanchy, WHO's in-house smallpox expert. The proposals would also permit

the two smallpox repository labs—one at the Centers for Disease Control and

Prevention in Atlanta and the other at Novosibirsk in Russia—to insert variola

genes one at a time into other viruses in the orthopox family, like monkey pox

and cowpox, Lavanchy wrote in E-mail to The Scientist.

 

Two other recommendations would allow the Russian and American teams to share

their smallpox samples with one another for the first time and to perform

experiments on variola and other orthopox viruses simultaneously, provided the

work is performed at the strictest biosafety containment level, BSL-4. Another

two propose that other researchers elsewhere be permitted to synthesize smallpox

fragments up to 500 base pairs in their labs but prohibited from synthesizing

longer ones and, with microarrays, permitted to include the whole variola

genome, just as long as individual array fragments are no longer than 80 base

pairs. The six recommendations the committee approved last week were all

proposed by its technical subcommittee in 2003.

 

C.J. Peters, director of the Center for Biodefense at the University of Texas

Medical Branch in Galveston, said he has reservations about the proposal to

allow individual labs to possess up to 20% of the entire variola genome. " If

they're going to send out big chunks of genome, I think that's a problem, " he

said, because different labs with different chunks " would only have to link them

together, and it would be a lot easier " to recreate the entire smallpox genome

than it would be to synthesize it.

 

Lavanchy said this was a " theoretical possibility " because not all labs would

receive exactly the same 20%. As a practical matter, however, he said, " this is

a rare request from a few labs working on that, and it's absolutely manageable. "

 

Richard Ebright, a professor at Rutgers University, said that a 10–15% threshold

would be preferable because " the 20% threshold corresponds to about 37,000 base

pairs, " which he believes is too large a number.

 

The rationale for the recommendation to allow scientists to insert any single

variola gene into any other orthopox virus is " to create a better model for drug

screening, " Lavanchy said. Because other orthopox viruses very similar to

smallpox can be worked on at lower containment levels than the BSL-4 that

smallpox requires, this proposal would allow faster and safer testing of

candidate drugs to cure smallpox, he said. The proposal would require the two

labs to ask WHO for permission separately for each variola-insertion experiment

they want to conduct, Lavanchy said.

 

The committee also recommended that the two labs be required to perform the

variola gene-insertion experiments at one higher biocontainment level than each

orthopox virus normally requires, to guard against the possibility that a

modified orthopox virus might be more virulent than the original one. The

concern is always around when you manipulate, " Lavanchy said. However, David

Evans, a committee member from the University of Alberta, said there is no

reason to think the modified virus would be more virulent.

 

Matthew Meselson, a professor at Harvard University, said he is unconvinced that

the proposed increased containment requirement will be sufficient to contain any

unexpectedly increased virulence. " You can't predict that, " he told The

Scientist. " There's always surprises. "

 

Meselson said that the proposal to require a one-level increase in containment

is an admission that the modified orthopox virus might be more risky than the

original. " Once you admit that, how can you say that one level is right? " he

asked. " Maybe half a level. Maybe two levels. Who's to say? That's not a

scientifically addressable topic. "

 

Although Ebright agreed that the single-gene insertion experiments may be

somewhat controversial among scientists, he pointed out that if adopted, the

recommendation would obligate WHO only to consider proposals for transfers, not

to necessarily approve them. For Ebright, the most important point about the WHO

committee's recommendations is to note the lack of similar international

oversight for other select biowarfare agents, like anthrax or Ebola.

Links for this article

R. Walgate, " Gene manipulation for variola? " The Scientist, November 12, 2004.

http://www.biomedcentral.com/news/20041112/01/

 

World Health Organization Advisory Committee on Variola Virus Research: Report

of the Fifth Meeting, Geneva, Switzerland, 4–5 November 2003

http://www.who.int/csr/resources/publications/WHO_CDS_CSR_GAR_2 004_15/en/

 

C.J. Peters

http://129.109.115.64/faculty/Peters/homepage.htm

 

J.D. Miller, " Interview with Richard Ebright, " The Scientist, 17:52, April 7,

2003.

http://www.the-scientist.com/yr2003/apr/prof2_030407.html

 

Matthew Meselson

http://www.mcb.harvard.edu/meselson/

 

Citation and Historiographic Analysis of Matthew Meselson Publications

http://garfield.library.upenn.edu/histcomp/meselson/

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