How do we know what causes an infectious disease? Part 1

We all know (or could guess given the spectacularly unimaginative naming) that salmonellosis (a type of food poisoning) is caused by Salmonella (a species of bacteria).  We know that because scientists say it is.  But how do they know?

A more general question: How do scientists prove that infectious disease ‘A’ is caused by bacterium ‘A’ and not by bacterium ‘Z’?

Let’s say I’m interested in an imaginary disease called chocolatitis ( a disease which forces its host to eat lots and lots of chocolate) which I suspect is caused by the also imaginary bacterium Chocolobacter.  But suspicions aren’t good enough, I want to prove it.

Well just over 100 years ago a physician called Robert Koch (with help and advice from his colleagues) came up with a set of guidelines or postulates that can be used to establish that a certain organism is the cause of a certain disease.  If I follow his guidelines I need to:

1) Establish that there is association of the organism with the disease.  Basically this means that in cases of chocolatitis is Chocolobacter usually there?  When a person/animal doesn’t have chocolatitis, is Chocolobacter usually absent?  Even if I’ve established this it could still be the case that having chocolatitis isn’t caused by Chocolobacter, it just makes it really easy for Chocolobacter to also get in to the host.  I can’t stop yet then, but must move onto…

2) Isolate the organism and grow it in pure culture.  So I need to take Chocolobacter from the infected person/animal and grow it (so you get lots of Chocolobacter), e.g. on a petri dish.  No other organisms should be growing on my petri dish – just Chocolobacter.  Lets pretend I’ve managed to do this?  Ok then next is …

3) Inoculate the disease into a healthy host and it should cause disease.  My once healthy host which I’m using for this test has come down with chocolatitis and all I’ve done to them is give them Chocolobacter so I’m now pretty bloomin’ confident that Chocolobacter causes this disease but just to check…

4) Reisolate the organism from the diseased host and show it is identical to the organism you got in 2).  This is basically the final check that it really really is Chocolobacter that causes chocolatitis. And yay, in my imaginary world the Chocolobacter I get out is identical to the Chocolobacter I put into my healthy host.

Because I have fulfilled all of these guidelines I have now established that Chocolobacter causes chocolatitis.

But it’s not always that easy.  Even Koch himself recognised that most of the postulates are not universal and so should be treated more like guidelines.

Some infectious agents can be carried by hosts without the host experiencing any signs of disease – these are “asymptomatic carriers”.  This messes up postulate 1 (it would mean that I could find Chocolobacter in healthy hosts as well as unhealthy ones).

Some agents are really difficult to isolate and culture. If the causes of chocolatitis was a virus it would be much harder for me to isolate it and grow it.  There are still some organisms that we know exist (we can pick up their genetic sequence – more on that in part 2) but that we still can’t culture in the lab.

Just as we can find infectious agents in healthy hosts, if you put an infectious agent into a healthy host it may not cause disease in them even if this agent causes disease in other hosts.  It might be that Chocolobacter is only dangerous to hosts with a suppressed immune system and so if I put it into a healthy host nothing would happen.

But although they are not hard and fast rules, they are still useful in that if the body of evidence supports my suspicion that chocolatitis is caused by Chocolobacter I can start to be more confident that my suspicion is correct.

Luckily, science has come on a long way since Robert Koch’s day.  Scientists have taken his postulates and have adapted them to the technology that we have available to us now.  More on this in part 2.

Further Reading

Contagion: Historical views of diseases and epidemics – Robert Koch

The Nobel Prize in Physiology or Medicine 1905 – Robert Koch

Do it yourself testing of the postulates with wheat leaves

Image

Cartoon By Gaspirtz (Own work) [CC-BY-SA-3.0], via Wikimedia Commons