The last two stores of smallpox under review
May 15, 2011 5:54 PM Subscribe

Health ministers from the World Health Organization's (WHO's) 193 member states will meet this week to debate when to destroy the two last known remaining stocks of the virus that causes smallpox.

Both sides of the debate seem to have traction within the scientific community as well as the researchers who eradicated smallpox in the 70s, mostly focusing on these two articles for (PDF) and against the destruction. While internationally the United States and Russian governments are working hard (NYT) to convince the, mostly developing, member countries calling for elimination in the WHO of the stock's value.

For some history on the subject The Demon in the Freezer previously is the classic article which expounds on the likely undeclared stocks of military grade variola virus. It draws heavily from Biohazard (big PDF), a book by Dr. Kenneth Alibek who in 1992 defected to the United States and detailed the terrifying extent of the Soviet bio-weapons program.

Threat posed by errant bookmarks, previously

The WHO has also commissioned a review of the research done with the virus over the last 11 years (big PDF) to help with the debate.

posted by Blasdelb (34 comments total) 18 users marked this as a favorite

Take a picture, it'll last longer? Fascinating post.
posted by cavalier at 5:58 PM on May 15, 2011

the virus’ genomic information is available online and the technology now exists for someone with the right tools and the wrong intentions to create a new smallpox virus in a laboratory.

D'oh
posted by stbalbach at 6:13 PM on May 15, 2011 [1 favorite]

Three days later, the aliens invade. Their only weakness?

Smallpox.
posted by The Whelk at 6:14 PM on May 15, 2011 [13 favorites]

Given that there's already a smallpox vaccine, how big a deal is this?
posted by ZenMasterThis at 6:31 PM on May 15, 2011

Given that there's already a smallpox vaccine, how big a deal is this?

Just because the vaccine exists doesn't mean that everyone is vaccinated.
posted by JauntyFedora at 6:33 PM on May 15, 2011

Given that there's already a smallpox vaccine, how big a deal is this?

Not only that, but we have anti-virals to treat it, but if it were to break out again, it would be expensive and take rather a long time to create enough vaccine to immunize everyone again.
posted by empath at 6:34 PM on May 15, 2011

~~branch~~ part
posted by msbutah at 6:36 PM on May 15, 2011

For those wishing to keep some for future study, is it not possible to store a virus in pieces? Separately store the examples of the genetic material from the proteins and whatever else. You still have all the bits, but the virus has been exterminated (in a technical and philosophical sense).

Is that completely crazy?
posted by Jehan at 6:38 PM on May 15, 2011

Jehan

You're in the right ballpark but I think the best approach would be to mutate the strain slightly to severely weaken it or render it incapable of infection. For example in my work as I scientist I routinely create viruses for infecting mammalian cells that are based on feline HIV but are only capable of infecting cells once, and cannot produce more viron particles.

That way you have a bug that's for all intents and purposes smallpox but won't kill large amounts of people
posted by slapshot57 at 6:42 PM on May 15, 2011 [1 favorite]

cavalier - Take a picture, it'll last longer?

stbalbach - someone with the right tools and the wrong intentions

On preview, empath, too.

I wonder how practicable it would actually be to recreate virulent smallpox only from the original sequence - synthesizing the actual genome wouldn't be difficult, but to get that genomic material in a viral package might prove to be. Mix artificial smallpox genome with live cowpox vaccine, and see if it'll package the artificial genetic material?

There may be initial transmission differences (the protein coat on viruses is usually part of how they get into a cell in the first place) which may alter the production of subsequent generation smallpox virion.

Also, maybe it's because I'm a cynic but even if the last stockpiles of natural smallpox are destroyed, what about all the, even deadlier or more controllable, weaponized versions that were almost for sure developed?

Does anyone know the specifics of raising modern smallpox vaccine? Is it an attenuated virus or is it a bunch of peptides + adjuvant? If it's peptide, then getting rid of the original stocks of live virus isn't a loss.
posted by porpoise at 6:44 PM on May 15, 2011

Weren't they using a cowpox variant anyway?
posted by empath at 6:46 PM on May 15, 2011

The methods of modern smallpox vaccines are outlined in the review above. The way we eradicated it was by live vaccines.
posted by curuinor at 7:01 PM on May 15, 2011 [1 favorite]

Given that there's already a smallpox vaccine, how big a deal is this?

Not only that, but we have anti-virals to treat it, but if it were to break out again, it would be expensive and take rather a long time to create enough vaccine to immunize everyone again.

Yes, this was true once (I'm surely not the only one to remember some scare articles about smallpox bioterrorism in the late 90s-early 00s), but since 2002 there's been enough smallpox vaccine stored up to vaccinate the whole US.

You can see a chart here showing how much vaccine various countries had in 2005. Germany, France, the UK have enough for their whole populations. Other countries (including Canada and Australia), not so much.
posted by dd42 at 7:14 PM on May 15, 2011

Given that there's already a smallpox vaccine, how big a deal is this?

The Smallpox vaccine can have a lot of side effects. Most people aren't vaccinated against it anymore.
posted by delmoi at 7:17 PM on May 15, 2011

the two last known remaining stocks

Yeah, you want to hang on to the last known remaining stock, to have a baseline to compare against when the first unknown remaining stock is released by some zealot.
posted by orthogonality at 7:29 PM on May 15, 2011 [5 favorites]

We've sequenced the DNA, we can rebuild it whenever we want.

Can you determine everything about an organism from its DNA alone?

Would you bet your life on that?
posted by Faint of Butt at 7:35 PM on May 15, 2011 [1 favorite]

"Yeah, you want to hang on to the last known remaining stock, to have a baseline to compare against when the first unknown remaining stock is released by some zealot."

While I am generally in favor of allowing the CDC to keep doing its thing, we do now have the sequence of variola. We could use PCR with any number of primers generated from that sequence to figure out exactly what we would be facing. Even if we wanted to serotype the "novel" smallpox strain we could save the antigens against what we've got rather than the virus itself
posted by Blasdelb at 7:38 PM on May 15, 2011

Can you determine everything about an organism from its DNA alone?

It's probably gonna take a universe simulator to truly determine everything about smallpox from just inspecting the DNA — but his point was that we can recover smallpox itself from the recorded DNA. Assuming we've got a reliable sampling and there's no other information, there's no reason he shouldn't be correct.
posted by floam at 7:49 PM on May 15, 2011

We've sequenced the DNA, we can rebuild it whenever we want.

“We can rebuild it. We have the technology. We can make it better than it was. Better...stronger...faster.... killier.”
posted by blue_beetle at 7:50 PM on May 15, 2011 [1 favorite]

The problem comes from choosing to eradicate a branch of evolved life. What if the smallpox virus has a certain mechanism, unknown to us, that could be reverse engineered to fight other strains of viruses? Or some unknown operation of viruses that, given future technologies, we could better understand? It's the decision to choose to completely do away with something. Forever.

While I agree with you in spirit, in practice this sort of thing doesn't seem to happen very often. There are literally mountains upon mountains of incompletely (or incorrectly!) analyzed data in laboratories around the world that no one will do anything with. We like to keep the data and the elements around, in case we ever want to go back and run some other study, but the reality is that new data and new techniques almost always trump the old - at least in terms of time invested by researchers. I don't think the case of smallpox is very different here, at least on scientific research merits. There are a myriad of issues that could be debated regarding removal of smallpox caches, some of which have already been touched upon in this thread, but we shouldn't be too worried about whether having the virus around will allow us to prevent or cure related diseases in the future. While it may be a viable solution, there are likely other solutions that researchers would arrive at more quickly.
posted by scrutiny at 7:51 PM on May 15, 2011

In some ways, just having the DNA of this virus printed pieces of paper means Smallpox will never go extinct. There's always some possibility someone will use it to effectively transport the virus through time and space. If you really wanted to kill it, you'd need to burn everything, zero out hard drives.
posted by floam at 7:53 PM on May 15, 2011

This isn't just a theoretical issue. Inadequate laboratory controls led to the infection and death of Janet Parker (and incidentally the heart attack of her father and the suicide of her head of department). It's statistically certain if we retain stores of the virus there will be another error that leads to its release. We don't need it to produce vaccines; we could recreate it if we really wanted to; why keep it around?
posted by Joe in Australia at 8:06 PM on May 15, 2011

I'm conflicted. I get the feeling that there's a 90% chance no good will come of keeping smallpox, but making this our policy for deadly diseases means that we're bound to destroy some useful, interesting genes and mechanisms with the viruses.

Yes, I know the cliche in horror movies is that the scientists who insist on keeping dangerous things around for research are always making a huge mistake, but this isn't a movie. I trust we have security that can keep smallpox contained and safe.
posted by mccarty.tim at 8:15 PM on May 15, 2011

OP said it all with the word 'known'. What other stocks are floating around in some forgotten Ukrainian bunker complex? If someone were to release a new strain how fast would we be able to isolate it, develop a vaccine against it, sequence it, etc. if we couldn't go back to the old stocks to work on a vaccine?

We have the vaccine, the stocks are safe, and the one in a million (not in my mind) chance that someone, somewhere has a stock and may be modifying it is still quite a chance given what it could end up doing.
posted by Slackermagee at 8:27 PM on May 15, 2011

Smallpox vaccines aren't actually made from smallpox; they're made from cowpox, a related but less deadly disease.
posted by Joe in Australia at 8:45 PM on May 15, 2011

Do we actually have the technology to reliably synthesize an entire genome? I'm not up to date with molecular biology, but it seemed like only a few years ago that synthesizing small fragments of DNA was a pretty big deal.

The answer to whether the stocks should be destroyed appears to depend on the unknown threat of unknown stocks and whether we won't be any better prepared to handle an outbreak with continued research. I would tend to err on the side of research unless there's reason to think that we aren't able to effectively secure these known stocks or that our response to an accidental release wouldn't be adequate to contain it, both of which would seem to further validate any concerns about unknown stocks and the importance of additional research. Then there's the whole issue of limited resources and whether research on an eradicated virus is more valuable than, say, AIDS research (as brought up in the for article), but that's almost a separate debate.
posted by howlingmonkey at 10:09 PM on May 15, 2011

Do we actually have the technology to reliably synthesize an entire genome? I'm not up to date with molecular biology, but it seemed like only a few years ago that synthesizing small fragments of DNA was a pretty big deal.

Synthesising an entire human genome (3 billion letters) is beyond us at the moment, a bacterial genome (millions of letters) is very hard but had been done and a viral genome (a few thousand letters) is pretty trivial. Depending on your method, it'd cost a few $thousand and take a few days to a week.

Currently, the machines needed to do this are expensive, costing hundreds of thousands to millions of dollars, so you'd need to send the sequence off to an established company or large research institute. These people routinely check the sequences they've been asked to synthesise against a database of nasty pathogens, so anyone who actually tries to order the smallpox genome should expect to be answering some pretty intense questions from their local government.

Of course, this isn't a perfect system. A few years back, a US lab ordered fragments of the smallpox genome from a load of different suppliers,each small enough not to alarm them, then assembled them in the lab, just to show that it could be done. I assume that the security systems have since ben updated to prevent this, but the real fun will come in a few years. Several companies have viable cheap synthesisers in the works to be sold on the inkjet printer model: buy the machine for a coupe of thousand, then buy cartridges of reagents. The synthesis cost doesn't drop all that much, but you can have the machine in your own lab to do runs whenever you want. As they approach release, they're watching each other as usual, but mostly they're watching governments: the worry is that governments will see widespread, cheap DNA synthesis technology as a major security threat and license and regulate the technology out of commercially viable existence. The alternative is to burden the machines with some sort of hugely annoying DRM-like system, forcing it to phone home for permission before starting a synthesis run.
posted by metaBugs at 12:39 AM on May 16, 2011 [6 favorites]

My memory of the poxviridae is pretty poor (I haven't thought about them much since undergrad), but a bit of reading around over lunch confirmed my impression that just having the DNA probably isn't enough to go straight to making smallpox. With some viruses, you can just stick the DNA into cells and get packaged virus out a few days later, but with smallpox I think you'd you need to stick in the DNA alongside a bunch of viral proteins in order to get any virus replication going, which is a bit of a catch-22 if you're trying to start from scratch. Our cells are set up to detect and prevent the replication of viruses, so viruses have evolved elegant methods to get around those defenses. The system that smallpox uses works very well, but is dependent on a bunch of viral proteins that it normally imports to the cell alongside its own DNA.

This isn't insurmountable for a decent lab with experience in this stuff: it's not too hard to start with the viral DNA sequence and modify some cells to make those viral proteins themselves, then stick your viral DNA in there and let the modified cell support the start of the virus' replication. I do something similar to make a much friendlier virus as part of my job. So we can still start from the electronic DNA sequence and make smallpox, but it'd be a bit more fiddly than simply ordering the unmodified genome and setting up a bioreactor, requiring more testing and validation and therefore more time.
posted by metaBugs at 5:45 AM on May 16, 2011

metaBugs, exactly right, Variola, the causative agent of smallpox, is one of the larger viruses we know of. Generally the larger the virus the less dependent it is on host systems and the more systems it packs along. Variola replicates in the cytosol and not the nucleus, unlike most eukaryotic viruses, which means that it needs to pack along all of the DNA replicating enzymes it would need, much less all the stuff to shut down host metabolism, replace it with a viral metabolism, shut down host defenses, and properly regulate gene expression through the capsid which stays intact. With Variola, you'd likely have to modify say mousepox pregnant cells to try to get it to pack a smallpox genome and then plaque purify or plate it on human cells.

Interestingly, the techniques Dr. Church is working on that would make this possible would make this significantly easier. The genome of variola is 186 kbp or 186,000 letters, which is not very feasible but possible.
posted by Blasdelb at 7:37 AM on May 16, 2011

I wonder how practicable it would actually be to recreate virulent smallpox only from the original sequence - synthesizing the actual genome wouldn't be difficult, but to get that genomic material in a viral package might prove to be. Mix artificial smallpox genome with live cowpox vaccine, and see if it'll package the artificial genetic material?

Isolated poxvirus DNA can be transfected into cell lines and it will produce infectious virus. IT could be the case that there are odd modified nucleotides or weird single strand breaks that are necessary for replication, but some poxviruses have been cloned into bacterial artificial chromosomes and subsequently used to produce live virus
(cite [pdf]).

Synthesising an entire human genome (3 billion letters) is beyond us at the moment, a bacterial genome (millions of letters) is very hard but had been done and a viral genome (a few thousand letters) is pretty trivial. Depending on your method, it'd cost a few $thousand and take a few days to a week.

Poxviruses are in-between these, they have some of the largest viral genomes at ~ 196000 bp. Mycoplasma genitalium, one of the smallest bacterial genomes, is about 580000 bp for comparison.
posted by benzenedream at 9:29 AM on May 16, 2011

Smallpox virus given three more years
posted by Blasdelb at 10:46 AM on May 26, 2011

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The last two stores of smallpox under review May 15, 2011 5:54 PM Subscribe

The last two stores of smallpox under review
May 15, 2011 5:54 PM Subscribe