> Although the World Health Organization declared smallpox, a contagious and sometimes fatal infectious disease, eradicated in 1980, there have been longstanding concerns that the virus that causes smallpox, the variola virus, could be used as a bioweapon.
As I understand it, the variola virus's genome is known and it is possible to recreate it in a lab.
There are a lot more people who will soon have access to genome fabrication technology (there are already companies that do this as a service) than can break into a BSL4+ laboratory and steal one of the few remaining smallpox samples.
Would smallpox survive in a microscope slide? I remember my late grandpa had a microscope slide labeled smallpox in his basement. He was an old time doctor and had all sorts of neat things down there after he died. I don’t remember what happened but think the slide is still sitting in a storage shed or something. Always been curious about the risk of having such a slide.
No, if the slide was prepared for storage the sample would have been embedded in a preservative with the cover glass glued down around the perimeter. The sample would likely be mixed with a mixture of alcohol, glycerin, and acetic acid known as AGA to prevent decomposition, this would kill any bacteria or viruses in the sample.
I have a microscope from my uncle, also a doctor, which came with a ton of slides he prepared. If you don't know someone who had to build that collection of their own specimens in med school, you can get all kinds of prepared slides commercially:
You might like to hear about Henrietta Lacks, arguably the first immortal human being, now called HeLa. Her living cells are one of the most widely distributed living human tissue available, still alive, still replicating because they have activated telomerase, which means the cells are not 'aging' in the way normal human cells do. I think it's about $400 for about a vial's size of tissue.
I do notice that only the mucus membrane, blood, hair, sweat gland, and hair follicle slides specifically say they're from a human, the others could be from a pig or any other large mammal and it would be very hard to tell the difference. Were I buying an assortment of electronics and a few items were labeled with a brand name and others were unlabeled, I'd assume the unlabeled ones were generic.
Also, one cadaver can generate an awful lot of slides. Each slide requires on the order of a microliter (1/1000 of a milliliter) of material, and a good microtome can cut samples with a thickness of a few micrometers (1/1000 millimeters). Essentially all medical students go through an anatomy class involving the dissection of a cadaver, and Google says there are 3.8 million doctors in China, so even with a generous assumption of 20 students per cadaver and a static field (it's not) with 50-year careers, that's still several thousand cadavers per year.
The Chinese, in particular, have access to human organs and body parts at rates that are much higher than even opt-out organ donation countries (where organ donation after death is nearly 100% due to the opt-out nature of their system).
This strongly suggests that “organ donation” in China is as-needed and on-demand from political prisoners and ethnic/cultural undesirables.
Based on my minimal understanding, viruses are too small to be seen under an optical microscope regardless of lens quality. Interesting imaging is done with an electron microscope. I would therefore guess that slide is focusing on tissue damaged by smallpox, not of the virus itself. It is therefore likely that the virus was rendered inert as a result of the same processes that were used to preserve the sample.
> Although variolation eventually declined or was banned in some countries, it was still practiced in others. "Buying the smallpox" was still practiced in Sudan until the late nineteenth century. However, variolation survived longer elsewhere. During the World Health Organization's Smallpox Eradication Campaign, vaccination teams came across variolators in remote areas of Pakistan and Afghanistan and their samples were confiscated. In the early stages of the campaign, live virus was detected in some, but as the campaign progressed variolators could not replenish their stocks, and although virus particles were detected in some samples, very few contained live virus. Our knowledge about the survival of smallpox virus suggests that passage of time makes it extremely unlikely that any infectious samples have survived.
> Would smallpox survive in a microscope slide? I remember my late grandpa had a microscope slide labeled smallpox in his basement. He was an old time doctor and had all sorts of neat things down there after he died. I don’t remember what happened but think the slide is still sitting in a storage shed or something. Always been curious about the risk of having such a slide.
Not sure, but I'd hazard that someone driven enough to break into one of the few remaining facilities holding live stock of smallpox would also probably be willing to infect themselves with it so as not to worry about preserving it.
Take this comment with a grain of salt, but there was an episode of House where his patient dug up some old treasure chest and it had a bottle with smallpox sores and they got infected. I remember him saying the virus can lay dormant for a long time. I’d make a phone call or two and get that safely dealt with.
The Lancet had a series of articles in the early 1980s about smallpox in Egyptian mummies, and the risk to Egyptologists. As far as I remember, at least some mummy bodies were preserved in cool, non-dry surroundings which are the best conditions for maintaining viability of the virus. There were also letters about people finding envelopes in old desks containing saved smallpox scabs, and there was concern about the viability of organisms in those. Bottom line: no one really knows. (Always a good answer in medicine.)
The implication when noting that two laboratories retained samples of smallpox is that both the USA and the USSR (now russia) have almost certainly been researching bioweapon applications and defenses on this virus for forty+ years, now. Not that a third-party is going to steal the virus.
During the cold war, this was a polite way of saying "we know you have this capability, and guess what, so do we."
This announcement of a drug to treat smallpox is probably more about the reheating of the US/USSR cold-war again, than it is about a mission-impossible style caper with someone stealing a virus everyone already knows everything about.
Defenses perhaps, but I highly doubt that either country is still researching bioweapon applications. What's the point? They have nuclear and (latent) chemical weapons which are far more militarily effective and less likely to cause "friendly fire" incidents.
OK but this is assuming it isn’t a highly modified virulent strain of smallpox.
Which would be my main concern, because god knows what happened to Russia’s stockpile of weaponized smallpox after the fall of the USSR. It wouldn’t surprise me if some of that is still floating around somewhere in a freezer…
> Because smallpox is eradicated, the effectiveness of Tembexa was studied in animals infected with viruses that are closely related to the variola virus. Effectiveness was determined by measuring animals’ survival at the end of the studies. More animals treated with Tembexa survived compared to the animals treated with placebo. FDA approved Tembexa under the agency’s Animal Rule, which allows findings from adequate and well-controlled animal efficacy studies to serve as the basis of an approval when it is not feasible or ethical to conduct efficacy trials in humans.
That's a little disconcerting that there are viruses that are similar, that they're severe enough to kill the host, and that they're willing to use it in tests. Perhaps these viruses they're using aren't nearly as contagious? Or they're not transmissible to humans?
Vaccinia, the smallpox vaccine, is a very closely related virus. You infect someone with it, they maybe get a bad rash at worst, and then they are immune to many of the poxes. Cowpox can and has been used the same way, too. This is why vaccination is named after cows.
Some poxes are awful for the primary host. Camelpox apparently kills about a quarter of camels that contract it. Just like smallpox (humanpox?) kills about 25% of humans, actually. But camelpox rarely even infects humans, and is self-limiting when it does.
Monkeypox is bad in humans. Almost as bad as smallpox, but not as contagious.
(This kind of thing is why the UK has national-level contract tracing capabilities. Occasionally something shows up that's not particularly easy to spread, but bad enough that it needs stopping sooner rather than later. I think we've had a few SARS and MERS cases too.)
Coincidentally I just finished reading Biohazard by Ken Alibeck and while old news (circa 1999) it left me with no doubt that there are still stockpiles of bioweapons grade smallpox in military labs. This news is strangely reassuring given how low vaccine stockpiles are against these awful diseases.
It's weird how matter-of-fact people were about smallpox in some memoirs. Casanova's descriptions are revolting but everyone just went on with their lives. 14-day quarantines when traveling were annoying but common (though maybe those were for plague).
If smallpox-as-a-bioweapon is even a slight possibility why don’t we start vaccinating for it again? It seems like it would be much easier to prevent the problem at all rather than to try to respond to it.
The current smallpox vaccines stockpiled in the US use a live virus¹ and have a fairly high rate of serious side effects (1–2%) for a disease that doesn't currently exist. The vaccines are also still effective a few days after exposure to smallpox.
Also, the way the smallpox vaccine is administered is mildly gruesome:
> A droplet of ACAM2000 is administered by the percutaneous route (scarification) using 15 jabs of a bifurcated needle. ACAM2000 should not be injected by the intradermal, subcutaneous, intramuscular, or intravenous route.
If routine vaccination was re-started, the Modified Vaccinia Ankara – Bavarian Nordic strain would probably be used, it's a two-dose intramuscular injection, same scheduled as the Moderna vaccine, and is approved in the US under the name "Jynneos". No scarring either, I would assume. In an emergency, ACAM2000 is a single dose and there's a lot of it, so it would be used in people who's immune system is good enough.
I got the vaccine in the military, the needle isn't bad, it looks like a tiny lobster fork. The worst part about it is how the injection site turns into a dime-sized itchy blister that you can't scratch for a few days.
I think the main issue is that it’s not difficult to create a vaccine resistant variant, modifying smallpox is apparently quite easy. Also current vaccines are only effective for around 5 years. I read about this recently, his other book about Ebola is worth a read too:
In this case, probably multiple reasons: A weaponized version might be designed to work around current vaccines. Though we do stockpile them, just in case. Also they're live vaccines with not so great risk profiles. Assuming the vaccines were still effective against a weaponized version, with an off-the-shelf (literally) vaccine ready to go we could aggressively vaccinate every sick and symptomatic person and everyone those people even looked at, and pretty effectively stop mini outbreaks as they occur. It's actually the method that was used in some developing countries during the eradication campaign. So we have a (likely) effective alternative to mass vaccination.
Also the vaccination leaves a small scar, so there's that too. Then again, if you don't get vaccinated, get smallpox, and survive? You may be full of lots of little scars.
There's also probably some societal/political/social problems (or some other better word to fit this) to starting up vaccinations: it would seem strange to do it if we didn't have specific knowledge of a threat. Look at COVID: we know it's a threat and people don't get vaccinated. So with smallpox vaccinations you'll get some people who panic thinking there must be a threat, others saying if there's no threat then it's pointless and won't do it.
Also as we see from COVID (and if you look at the history of the polio vaccine along with the massive industrial complex around annual flu vaccines) it's clear that such efforts are truly & enormously massive and expensive and difficult. We can't really go around doing that for every potential threat.
Notably, what was approved by the FDA does not appear to be a vaccine, and is instead an anti viral medication effective against smallpox. Also notably, we don't truly know it's safety profile: it would be tough (and unethical) to infect humans with smallpox to try out the drug, so it was tested on animals and approved on the basis of those results. I guess if you want to develop medications against potential-but-not-yet-realized threats, that's the best you can do.
Because vaccination isn’t 0% risk. Very few people are going to acquiesce to vaccination for a functionally extinct virus nor should they. Perhaps those who want to should be able to but that’s another discussion.
If that describes you then you really need to be putting out some serious DPS, glass-cannon style. Otherwise you need bulk up on CON and figure out your dump stats so you can tank effectively for the damage dealers/buffers/de-buffers.
I'm confused by the FDA. So last June, there were 3 COVID vaccines that passed phase I clinical trials and animal challenge studies. There was an active pandemic raging, and vaccines were almost certainly had 100x less risk for those over 65 (a statistical no brained)
But somehow, they kept all vaccines banned for another 6 months killing hundreds of thousands. Nothing.
But in the last week they approved an Alzheimer's drug that basically doesn't work (they have 9 years to prove it) and a smallpox drug with no human studies.
Why couldn't we have unbanned the vaccines long before we did? Those that said we can't possibly approve something without following an exact process this week we're just totally proven wrong.
I think the bar for "not banning" should be lower. The bar for "medicare must pay infinity dollars for it" should be higher.
> FDA approved Tembexa under the agency’s Animal Rule, which allows findings from adequate and well-controlled animal efficacy studies to serve as the basis of an approval when it is not feasible or ethical to conduct efficacy trials in humans.
Vaccines are usually tested for a much higher standard because
It's generally taken by a LOT of people and to PREVENT something. It's a proactive medicine rather than reactive. FDA is a lot less strict with reactive medication, especially in cases where the disease is just fucking awful.
This is also the technical reason why male birth control hasn't hit the market yet. They don't consider pregnancy to be an issue for men, but do for women. Hence they tolerate the side effects of BC for women a lot more.
> Complications of smallpox included encephalitis (inflammation of the brain), corneal ulcerations (an open sore on the clear, front surface of the eye), and blindness.
A tragic reminder of the horror inflicted on indigenous people by the colonies that would become the United States. A bioweapon used to craft the narrative of the empty, pristine continent, bestowed by God for the fulfillment of Manifest Destiny.
One doesn't have terribly much to do with the other. Smallpox was introduced to the Americas in 1520. The only recorded attempt to deliberately infect Native Americans with it was in 1763 by a British officer. By 1803 the US government was already running smallpox vaccination programs for the Native American tribes with which they had contact. Not that the later Manifest Destiny actions weren't horrific and devastating, but they had nothing to do with creating an idea of a clean continent using disease. 19th century Americans were more than happy to invade and seize land that was fully inhabited.
The Brits of that era were equal-opportunity smallpox infectors. They captured some of George Washington's slaves, infected them with smallpox, and then released them on the battlefield at Yorktown, hoping to spread disease back to GW. They also brought smallpox into the American camp before the battle of Quebec, and there was an epidemic.