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Date: Sun, 28 Apr 1996 18:56:01 -0400 (EDT)
From: "Ian A. York" <iayork@panix.com>

I append a bit of smallpox info. I think the final vote for destruction of the stocks in coming up in a few weeks - I'll send an update when I hear about that; the stocks will most likely be destroyed in the next year, if not the next month.

bio-war.

As a conspiracy theory this is unanswerable, as are all conspiracy theories. What I can do is point out that there were and are legitimate scientific reasons for not destroying the smallpox stocks, and that the objections of scientists were what held up the destruction. I can also point out that while smallpox is an excellent weapon for terrorists - because of the emotional associations - in fact it's not so good for warfare, and the US and USSR most likely have far better biowarfare weapons. Moreover, there's no point in keeping smallpox as *protection* against the other side using it, as I mention below.

The fundamental point is that smallpox, as a disease, has been eradicated from the world, and yet the US and the USSR both have stocks of smallpox virus. The World Health Organization has called for the destruction of these stocks several times, and they still haven't been destroyed. Arguments for the scientific value of the smallpox stocks were weakened when the entire smallpox genome was sequenced (Virology. 201(2):215-40, 1994) - that is, all 186,102 base pairs that form the smallpox DNA are known and stored in databases. I append the WHO press release from Sept. 1994 discussing this recommendation.

However, this recommendation was controversial: several virologists are strongly opposed to destroying the stocks. Much of the debate has been published in the journal Science:
Mahy BW. Almond JW. Berns KI. Chanock RM. Lvov DK. Pettersson RF. Schatzmayr HG. Fenner F.
The remaining stocks of smallpox virus should be destroyed. Science. 262(5137):1223-4, 1993

Joklik WK. Moss B. Fields BN. Bishop DH. Sandakhchiev LS. Why the smallpox virus stocks should not be destroyed. Science. 262(5137):1225-6, 1993

Baltimore D.
Smallpox virus stocks.
Science. 263(5143):13, 1994

Turner WJ.
Smallpox virus stocks: more votes
Science. 263(5149):903-4, 1994

For those of you who don't recognize the names of these authors, we're talking Battle of the Giant Virologists here. Nobel prizes out the wazoo. Fenner is the editor of one of the definitive virology texts, Fields is the editor of the other, Bernard Moss is the poxvirus God, David Baltimore is David Baltimore, and most of these other guys have a bunch of books, and hundreds of papers, to their credit.

There was also a public debate at the American Society for Virology conference in 1993. Although I was at that conference, I didn't go the debate (I was drinking a few beers with other lowlifes). I'm not dumb enough to get up and argue with Bernard Moss: he'd think me into a bloody pulp. Anyway, I heard afterward that it was a rousing free-for-all, lasting for hours, and I'm sorry I missed it even though no fisticuffs - quite - flew.

A lot of people seem to think this has something to do with vaccines: they are wrong. Smallpox itself is not used at all for smallpox vaccination - the vaccinia virus is used for that, and vaccinia is not going to be destroyed. (In fact, vaccinia is a very widely used virus - just about every lab I've been in has used it to some extent.) In particular, the vaccine stocks are explicitly going to be kept, as the WHO press release makes clear. That means that those people who think the stocks of smallpox should be kept in case (for example) a body carrying smallpox virus is preserved in the antarctic ice resurrects smallpox are off target. It's also the reason why there's no point in keeping smallpox as protection against an opponent using it; there lots of vaccine around, and the vaccine is extremely effective.

So what is the scientific usefulness of smallpox virus? The bottom line is that smallpox is highly virulent, while vaccinia is almost non-virulent - but vaccinia and smallpox are very similar viruses. Many of the genes are more than 90% similar between them. This means that there's a very unusual opportunity to identify the molecular basis of viral virulence - and that's a field which is immensely important, and very poorly understood. If vaccinia has a gene that looks like THIS, and smallpox version of the gene looks like THAT, then maybe that's why vaccinia is a more efficient virus. (Sic. Obviously vaccinia is a more efficient virus - it's alive, and smallpox is almost dead.) I won't go into details, but although it's useful to have the genome sequence, the whole virus can't be understood from that. There are many complexities that can only be sorted out from the intact virus.

So the bottom line is that there are solid scientific reasons for keeping smallpox, and the people arguing for keeping it are top-notch scientists from many different countries - not just the USA. The reasons for destroying it are also compelling, though, and I (and probably the majority of virologists) think that's the way to go. The final vote is coming up very soon and will almost certainly confirm that the stocks will be destroyed; I'll update when that happens.

Ian

Press Release WHO/65 - 9 September 1994

SCENE IS SET FOR DESTRUCTION OF SMALLPOX VIRUS

The last remaining stocks of smallpox (variola) virus should be destroyed, says a WHO international group of experts. This was the unanimous verdict pronounced today by the Ad Hoc Committee on Orthopoxvirus Infections during its final one-day meeting here in Geneva. This confirms the recommendation of the preceding Committee meetings, in March 1986 and December 1990.

A majority of the Committee agreed that the time of destruction should be 30 June 1995, allowing the World Health Assembly to confirm this recommendation at its meeting of May 1995. The stocks include clinical specimens and other materials containing infectious variola virus. These materials are being held in the WHO Collaborating Centres for Smallpox and other Poxvirus Infections in the Centres for Disease Control and Prevention in Atlanta, Georgia, United States of America and in the Institute for Viral Preparations in Moscow, Russian Federation. Recommendations on the procedure for destroying the variola virus and for the certification of its destruction were also issued.

Cloned DNA fragments of variola virus genome are themselves not infectious and provide a useful resource for analysing variola virus genes and protein structure and function. The members of the Ad Hoc Committee recommended that such cloned material be kept. The Committee recommended the establishment of two international repositories for the storage, distribution and monitoring of the cloned material - at the WHO Collaborating Centre for Smallpox and Other Poxvirus Infections, CDC, Atlanta, and at the Russian State Research Centre of Virology and Biotechnology in Koltsovo.

The Committee also recommended that smallpox vaccine (500,000 doses) be kept by WHO in case of an emergency and that the vaccine seed virus (strain Lister Elstree) be maintained in the WHO Collaborating Centre on Smallpox Vaccine at the National Institute of Public Health and Environmental Protection in Bilthoven, The Netherlands.

Commenting on the results of the meeting, Dr Ralph Henderson, WHO Assistant Director-General, said: "The Ad Hoc Committee had a very difficult task before it. The basic problem was to weigh the potential risks of this virus escaping with the potential benefits to science from retaining it. This is a matter of best judgement, not scientific certainty. The next step is to seek as broad a consensus as possible concerning this recommendation. We will be doing this by widely publicizing the Committee's recommendations and by asking them to be reviewed by the WHO Executive Board in January 1995 and put for final decision to the World Health Assembly in May 1995."

The eradication of smallpox is among the greatest public health achievements of all time. This success resulted from an unprecedented international effort coordinated by WHO and was recognized by the 33rd World Health Assembly which declared on 8 May 1980 the global eradication of smallpox. The last known natural case of smallpox was detected in Somalia in October 1977.

Less than 30 years ago, smallpox was endemic in 31 countries. At that time, between 10 and 15 million people were stricken with the disease each year: of these nearly two million died and millions of survivors were disfigured or blinded for life. Smallpox was the first disease ever to be eradicated.

Since that time, the stock of variola viruses has been gradually reduced and is now restricted to two WHO Collaborating Centres at the Centres for Disease Control and Prevention in Atlanta, and at the Institute for Viral Preparations in Moscow.

The concept of total global eradication calls not only for the elimination of the disease but also for the complete removal of the causative agent. During their first meeting in March 1986, members of the WHO Committee on Orthopoxvirus Infections unanimously recommended destruction of the virus stocks kept in the two laboratories.

The Committee also recommended however that the genetic blue-print of the variola virus should be determined and archived prior to destruction of the remaining stocks of the virus. In order to further understanding of this highly virulent virus and to be able to conduct proper diagnostic tests, if need be, it was decided to carry out complete sequencing of the genome.

At the end of the last meeting of the WHO Technical Committee on the Analysis of Nucleotide Sequences of Variola Virus Genomes, held in Geneva in January 1994, Dr Bernard Moss, of the National Institute of Health in Bethesda, Maryland, United States of America, concluded: "Now we are fully satisfied that the genetic blue-print of variola virus has been properly archived for posterity. Should the need arise, we will be able to conduct diagnostic tests with 100% accuracy".

The publication of the Ad Hoc Committee's recommendation to destroy the variola viruses had, however, triggered mixed reactions from both the public and the scientific community. The arguments for and against destruction can be summarized as follows: Against destruction:

• all possibility of future studies on the virus will be lost;
• destruction of the viruses in the two known repositories does not guarantee the complete removal of the virus from the earth (preserved corpses of smallpox cases, forgotten or hidden stocks elsewhere);
• the decision to destroy the virus is politically, and not scientifically, motivated.

For destruction:

• the escape of the virus from the laboratories from the laboratories and its use for terrorist purposes would be a serious risk as an increasing proportion of the population lack immunity to the disease;
• the sequence information and the cloned DNA fragments of full genome of several strains of variola virus allow further scientific research on the properties of the viral genes and proteins to continue. The cloned DNA fragments of the virus genome are non-infectious and can be handled in complete safety.
• the decision to eradicate smallpox was a collective decision of the world community, based on public health considerations. Eradication is an absolute term and includes not only the elimination of the disease, but also the complete removal of the causative agent.