Of Mice and Men

It’s not always easy figuring out how a pathogen causes disease.   There is an example in mice for which the solution was very difficult, so difficult that we would probably have failed to discover the cause of a similarly obscure infectious disease in humans.

Mycoplasma pulmonis causes a chronic obstructive lung disease in mice, but it wasn’t easy to show this.  The disease was first described  in 1915, and by 1940, people began to suspect Mycoplasma pulmonis  might be the cause.  But then again, maybe not.  It was often found in mice that seemed healthy. Pure cultures of this organism did not consistently produce lung disease – which means that it didn’t satisfy Koch’s postulates, in particular postulate 1 (The microorganism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy organisms.) and postulate 3 (The cultured microorganism should cause disease when introduced into a healthy organism.).

Well, those postulates are not logic itself, but rather a useful heuristic.  Koch knew that, even if lots of other people don’t.

This respiratory disease of mice is long-lasting, but slow to begin. It can take half a lifetime – a mouse lifetime, that is – and that made finding the cause harder.  It required patience, which means I certainly couldn’t have done it.

Here’s how they solved it.  You can raise germ-free mice.  In the early 1970s, researchers injected various candidate pathogens into different groups  of germ-free mice and waited to see which, if any, developed this chronic lung disease. It was Mycoplasma pulmonis , all right,  but it had taken 60 years to find out.

It turned out that susceptibility differed between different mouse strains – genetic susceptibility was important.  Co-infection with other pathogens affected the course of the disease.  Microenvironmental details mattered –  mainly ammonia in cages  where the bedding wasn’t changed often enough.  But it didn’t happen without that mycoplasma, which was a key causal link, something every engineer understands but many MDs don’t.

If there was a similarly obscure infectious disease of humans,  say one that involved a fairly common bug found in both the just and the unjust, one that took decades for symptoms to manifest – would we have solved it? Probably not.

Cooties are everywhere.

 

 

 

 

 

 

 

 

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20 Responses to Of Mice and Men

  1. The fourth doorman of the apocalypse says:

    Somewhat OT, but this study on the effects of crack-cocaine addicted mothers on the average IQ of their offspring seems to have some surprising insights, but perhaps not what the author claims.

    Eg, perhaps if you already have a low IQ then being a crack-cocaine addicted mother won’t have much effect on your offspring (average of 81 for the control group vs average of 79 for the addicted group.) It also seems to confirm what 100 years of testing tell us about the average IQs of a certain group.

  2. The average years of survival beyond 60 didn’t move up much until quite recently. (Lower life expectancies were an average, and largely the result of diseases in infancy and childhood, as Greg pointed out a couple of months ago.) But now the game has changed, and there actually is an increase in the percentage of people living to 80, 90, 100. Because of this we die of some different things, such as cancers – some of which are clow to develop. In the Good Old Days, you died of something else before the cancer matured.

    I think of this when I listen to those who are quite certain we are soon destined to live not only to 120, but twice that, of even indefinitely, according to Aubrey de Gray. Perhaps I am merely cynical, but I suspect we’ll keep finding lots of new stuff to die from. And some of it may be hard to fix.

    • gcochran9 says:

      We know a little about second-order old age from studies of supercentenarians.

      It looks as if transthyretin amyloidosis is a major factor. Transthyretin is a carrier for thyroid hormones: misfolded versions result in long, sticky fibers that accumulate on the interior of blood vessels. It can cause peripheral sensory neuropathy and cardiomyopathy, and you’re likely to get it by 110. One more thing to worry about.,

      I wouldn’t rely on Aubrey de Gray.

      It might be easier to fix if we invested more than a millionth of a percent of GNP on longevity research. It’s doable, but hardly anyone is interested. I doubt if most people, including most MDs and biologists, even know that it’s theoretically possible.

      I suppose I should do something about it. Some of our recent work ( Henry and me) suggests that people of sub-Saharan African descent might offer some clues – their funny pattern of high paternal age probably causes the late-life mortality crossover, it couldn’t hurt to know the mechanisms involved.

  3. bruce says:

    >Cooties are everywhere.

    In some invertebrates (especially insects) the male cements up the female genital opening after copulation to prevent other males from fertilizing her. The males of Moniliformes dubius, a parasitic acanthocephalan worm in the intestines of rats, produces a chastity belt of this kind but in addition to sealing up the female after copulation, the male sometimes ‘copulates’ with rival males and applies genital cement to prevent them from mating again (Abele and Gilchrist 1977).

    Got rat cooties?

  4. Greying Wanderer says:

    http://en.wikipedia.org/wiki/Herpes_simplex

    “It is said that Emperor Tiberius banned kissing in Rome for a time due to so many people having cold sores.”

    “In the 16th century Romeo and Juliet, it is mentioned that there are blisters “o’er ladies’ lips.” In 18th century it was so common among prostitutes that it was called “a vocational disease of women.””

    Imperial centres.

  5. The fourth doorman of the apocalypse says:

    But Mousie, thou art no thy-lane
    In proving foresight may be vain
    The best laid schemes o’ Mice an’ Men
    Gang aft agley
    An’ lea’e us nought but grief an’ pain
    For promis’d joy!

  6. pauljaminet says:

    I believe the vast majority of chronic diseases are of this type — caused by chronic infections; also caused by malnutrition, toxins, and unhealthy lifestyles that impair immunity and repair of disease damage; and hastened by genetic backgrounds which are beneficial against some infections but harmful against others.

    There are a large number of known disease-infection associations, in which the prevalence of the disease is much higher if you are infected with a certain pathogen. Russ Farris has documented hundreds of these associations I believe.

    The technology exists to enable research into chronic infections, develop diagnostic tests, and develop pathogen-specific therapies. But there is distressingly little such research performed — no money for it, many regulatory barriers. Medicine and biomedical research spend $2 trillion a year, nearly all unproductively.

    • bruce says:

      Louis L’Amour said people who live on mountains tend to live longer. Lower air pressure, lower heat- why don’t hospitals provide this?

      • pauljaminet says:

        Fewer insects (mosquitos, ticks) is probably the major advantage. In general colder temperatures, if there is no loss of sunshine and vitamin D, are beneficial. Mountains are cold but high UV / high sunshine environments. Less oxygen is probably helpful too. And less pollution.

  7. Timtoc says:

    Tuberculsois is a pathogen that prefers high ambient oxygen concentrations. Physicians often recommended either a sea voyage or a stay in the mountajns for sufferers of consumption. I am not aware of controlled trials on this matter.

  8. Magus says:

    Greg, I was curious, if some billionaire decided to pour his funds into investigating your hypothesized virus that causes male homosexuality:

    1- what do you think would be most cost effective way of spending said funds to that regard
    2- how much (ballpark figure, or range) do you think would be necessary to have a decent probability of success (50 million? 500 million? more?)
    3- what time horizon do you think we’d be talking about for said investigation/discovery (10 years?30years?)

    • gcochran9 says:

      It’s hard to say, depends on how complicated the path of causation is. Assuming that I’m even right, of course. Some good autopsy studies might be fruitful – you’d look for microanatomical brain differences, as with nartcolepsy. Differences in gene expression, maybe. You could look for a pathogen – using the digital version of RDA (representational difference analysis), say on discordant twins. Do some old-fashioned epidemiology. Look for marker antibodies, signs of some sort of immunological event.

      Do all of the above on gay rams – lots easier to get started, much less whining from those being vivisected.

      Patrick Moore found the virus causing Kaposi’s sarcoma without any funding at all. I’m sure Peter Thiel could afford a serious try.

  9. Anonymous says:

    Has Roselli used discordant twin rams in any of his studies?

  10. Greying Wanderer says:

    If it was a bug that could be passed both sexually and from mother to child and which effected the brain and/or nervous system then the Chinese govt might be interested in researching it given their std epidemic.

    http://www.biomedcentral.com/1741-7015/9/111

    • Anonymous says:

      GW…are you suggesting that every gay male was buggered as a baby?

      • Greying Wanderer says:

        “could be passed both sexually and from mother to child

        I’m not sure how that could have been any more clear.

        If it was an STD (and it’s just one option) then it would need to meet certain conditions
        – pass heterosexually and homosexually
        – pass mother to child
        – effect nervous system or brain
        – be fairly widespread but only cause homosexuality in conjunction with other factors (as per the example in this thread)
        – be relatively recent in northern europe (centuries)
        – flare up and die out
        etc

        For people who don’t get it the main reason for stressing the possibility of an STD – China isn’t PC and *if* it is an STD China is going to find itself very ****ed indeed over the next couple of decades.

  11. Greying Wanderer says:

    http://news.nationalpost.com/2013/07/30/rare-condition-makes-james-bond-theme-music-orgasmic-for-man-who-suffered-stroke/

    The stroke occurred in his thalamus — the walnut-sized area in the middle of the brain that acts as the brain’s main relay station for sensory information, and that’s tightly packed with bundles of nerve fibres connecting different brain regions.”

    In the process of trying to repair itself, the man’s brain miswired, so that areas that would normally never be connected were suddenly “talking” to each other, Schweizer said.

    “It’s rewiring gone awry.”

    A bug might be common and cause a common form of damage that leads to various forms of uncommon mis-repair?

  12. Pingback: Militantni ateizam = puritanska kršćanska hereza | Nekompetentna reakcija

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