Oh, the things researchers get people to do in the name of Science…

When most microbiologists talk about poop, they are talking about bacteria. Salmonella, E. coli, Cholera– they have all evolved different, wonderfully complex ways of making people poopy.

But if you really want to make a lot of people poop, and fast, you need a virus!

While we get a pathogenic Salmonella outbreak every now and then, GoogleNews ‘norovirus’ real quick. You can find tons of current articles on outbreaks on cruises, parties, schools, weddings– This bastard is everywhere, all the time, ruining peoples good times. Like other non-enveloped viruses (ie polio), noroviruses are tough bastards that require special cleaning/cooking protocols to ensure the buggars are dead. So when those protocols arent followed, noroviruses spread like wildfire.

But despite all the diarrheal damage noroviruses cause, we didnt even know they existed until very recently. We thought enteric diseases were caused by bacteria… but then in the 1940s, scientists filtered poop from infected individuals (cell free=no bacteria) and got volunteers to swallow it. I shit you not. These volunteers subsequently got sick too.

So, something smaller than a bacteria, ie, a virus, was causing the illness.

But the actual virus wasnt identified until 1972, when scientists got volunteers to swallow cell-free poop once again after an outbreak in a Norwalk, Ohio elementary school. Scientists used the volunteers antibodies to get the virus to clump together to get chunks they could visualize with electron microscopy. Importantly, the clumps didnt form with pre-infection sera, thus, the apparent virus that these antibodies were sticking to was the etiologic agent behind non-bacterial enteric disease. So thats how noroviruses got the nickname ‘Norwalk virus’.

But even now that the scientists knew what they were dealing with, they couldnt get the virus to grow in tissue culture. Like, with HIV-1, I can get a ton of virus in 48 hours with an infectious molecular clone. Or you can just throw virus on white blood cells from volunteers, and in a week, youve got a ton of HIV-1 in your flask. No big whoop.

These tricks dont work with noroviruses.

So, to get enough virus to characterize its genome, scientists fed volunteers yet more poop, collected their poop, and purified the viral RNA. By 1990, we had the Norwalk virus sequence!

Now, this is a lighthearted post, but many people (especially children/elderly) die from bacterial/viral enteric diseases. Sure, poopy is funny. Dead, dehydrated babies, not so much. So obviously we are trying to make a vaccine.

Unfortunately, it appears that none of us have long-term immunity to noroviruses. After feeding volunteers filtered poop, scientists discovered that after an infection, you are protected from another infection for a couple of weeks. But then youre right back to being just as susceptible as you were in the first place.

Some volunteers drank the filtered poop and didnt get sick… but scientists cant figure out why. Seems it has nothing to do with the concentration of norovirus-specific antibodies in your system, because some of the people who didnt get sick didnt have any norovirus antibodies… an unfortunate, unexpected stumbling block for vaccine developers.

To make matters worse, we cant even get an animal model going. Scientists have fed poop to mice, guinea pigs, rabbits, cats, cows, baboons, rhesus macaques, marmosets, owl monkeys, patas monkeys, cebus monkeys, chimpanzees, mangabeys, and pig-tailed macaques… they dont get poopy. Only humans get poopy.

There is some hope in the recent discovery of a murine norovirus, but for the time being, it seems we still need to rely on the generosity of volunteers who dont mind pooping a couple days for The Greater Good.

Comments

  1. #1 ceestar42
    July 8, 2009

    Ugh, norovirus. My sister worked in a daycare and a wave of that came through. They had to close, send everyone home, and scrub the facility down. The health department person who first came through then got sick, and so when it was time for the official “all clear” the health department person (a different one) refused to come inside!

  2. #2 Mind Over Splatter
    July 8, 2009

    “Only humans get poopy.”
    See, we are special ! ; )

  3. #3 jdoug
    July 8, 2009

    One Prof at my old department is working on an animal model using a new murine norovirus. Here’s her page http://www.lsuhscmicrobiology.com/karst.htm
    Like i said it’s not a human virus but it’s a start :)

  4. #4 W. Kevin Vicklund
    July 8, 2009

    Wow, this sounds like WW’s dream job: feeding people shit.

  5. #5 The Curmudgeon
    July 8, 2009

    The virus appears to be irreducibly complex and specifically designed for humans. This tells us a great deal about the Designer. It also explains why the UFO abductors are always probing their captives. Abbie, you’re on the cusp of a breakthrough!

  6. #6 sinned34
    July 8, 2009
  7. #7 Prometheus
    July 8, 2009

    “….scientists filtered poop from infected individuals (cell free=no bacteria) and got volunteers to swallow it. I shit you not.”

    Erv should get together with the gang over at Barf Blog.

    http://barfblog.foodsafety.ksu.edu/

    She would be like Dorthy Parker at a Bizzaro World Algonquin Round Table.

  8. #8 Sili
    July 8, 2009

    Somehow I think the information shit for the volunteers didn’t say “filtered poop”.

    But it is awefully nice of people to do this stuff in the name of Science. I only lent my liver for research (and was paid nicely for it).

  9. #9 Eric
    July 8, 2009

    Your post made me smile – I’m an epidemiologist, and there’s a soft place in my heart for the gastroenteritis-causing viruses of the world.

  10. #10 BeamStalk
    July 8, 2009

    “You eat pieces of shit for breakfast?”

    Sorry I couldn’t help the Happy Gilmore quote.

  11. #11 SLC
    July 8, 2009

    OT but perhaps not so much considering the theme of this post. Francis Collins was named Director of the NIH minutes ago.

    http://www.bloomberg.com/apps/news?pid=20601087&sid=atJa8QDGj8QU

  12. #12 Joshua Zelinsky
    July 8, 2009

    Ok, dumb question, do other primates not even have analogs of the human noroviruses? It seems sort of strange that a whole class of viruses would only infect us.

  13. #13 Optimus Primate
    July 8, 2009

    I wasn’t going to do it, but since this post’s Adam Sandler-quoting cherry has already been popped:

    “She called the shit ‘poop’!”

  14. #14 ERV
    July 8, 2009

    Josh– Norovirus isnt a class, its a genus :P And its a genus with only one extremely genetically diverse species. Virus taxonomy w00t!

    But its not weird to have a virus that can only infect humans. We would have never been able to eradicate smallpox/polio if there were always reservoirs in other organisms!

    And its not just viruses– some of the really bastard bacteria (Salmonella typhi) only infect humans too.

  15. #15 Rogue Epidemiologist
    July 8, 2009

    Ahh, noro. It makes up the brunt of my work in the winter. It’s such a tough virus — short of killing it with fire, you had better be using Clorox.

    Here’s a best-of list of culprits epidemiologically linked in noro outbreaks I’ve investigated:
    Ice cream with fresh berries
    Muffins
    Fruit salad
    A traveling soccer team
    A gaggle of sorority girls (actually we’ve had three sorority outbreaks — no frats, though!)
    A pastry chef
    Banana bread
    And a guy who was working at two restaurants, causing simultaneous outbreaks at both, with secondary AND tertiary cases (we presented that investigation at APHA last year)

    fun, fun, fun! These days, it is natural for me to flee a bathroom if I ever hear someone puking in one of the stalls. Noro aerosolizes like mad!

  16. #16 eddie
    July 9, 2009

    Sorry to be a bit of a party pooper but looking for an animal model for norovirus seems too much like searching for dropped keys under the lamp-post.
    As the current alternative is drinking the stuff, Id suggest maybe a better alternative might be a simulated human gut in vitro.
    It’d be a modern extension of Fleishman n Ponz (sp?)

  17. #17 eddie
    July 9, 2009

    Aaarrrggghhh!!!
    I meant Miller-Urey, honest!
    Was that a freudian slip?

  18. #18 BAllanJ
    July 9, 2009

    Good, ’cause I was kinda wondering how cold fusion was coming into this. Not that F&P saw cold fusion, or anything…

  19. #19 stogoe
    July 9, 2009

    I thought maybe you were talking about the sculpture that digests food and poops it out.

  20. #20 eddie
    July 9, 2009

    stogoe, yes. Seems like the idea is used as art but would be great for microbiology research.

  21. #21 eddie
    July 9, 2009

    Check out http;//www.cbc.ca/arts/artdesign/story/2009/01/17/montreal-sculpture-cloaca.html
    If an artist can get this far with the idea, theres no reason every university in the world can’t make one, and use it for research into everything from noro to bio-methane power.

  22. #22 Joshua Zelinsky
    July 9, 2009

    Abbie, thanks for that (and yes, I really shouldn’t have used the word class). Didn’t realize that the noroviruses were only a genus though. Interesting. Although regarding polio, and smallpox there are in both those cases very similar viruses that can infect non-human species, right?

  23. #23 Brian Foley
    July 9, 2009

    In the case of Noroviruses, there are almost certainly non-primate species besides the mice that carry them. There is quite a bit of diversity in the human Noroviruses, and evidence of recombination between different human Norovirus lineages. No evidence of human-mouse or mouse-human cross-species transmissions. As someone said above, it is like looking for keys under the lightpost because that is the only place where there is light enough to see them. If Noroviruses are carried asymptomatically by dogs, or deer, or seals, or birds (and who would notice the symptoms in a goose, anyway?) we would never detect them.

  24. #24 J Todd DeShong
    July 11, 2009

    Sorry, ERV, but this post made me a Norovirus Denialist. You did it to me. It’s your fault. By your own words the norovirus can’t be cultured, there’s no animal model…all just like HIV! That settles it, then, norovirus do not exist! hehe NOTE: Kidding!
    JTD

  25. #25 Cat Faber
    July 12, 2009

    All I can say is I am profoundly grateful for those courageous and self-sacrificing volunteers, deliberately drinking filtered poop so they could get sick and produce more virus for scientists.

    You don’t see altruism like that very often.

  26. #26 Bacopa
    July 26, 2009

    I’ve sometimes wondered if something like norovirus or rotovirus might be responisble for some cases of wet tail in hamsters. Where can I buy a fecal filter so I can test this hypothesis? How can I practice such secure infection control that I can rule out every source of infection except filtered poop?