Going From Correlation Studies to Causation Studies

KOCH’S POSTULATES are a set of criteria that, if achieved, prove that a specific microorganism is pathogenic, hence can be used to prove whether a Plasmodium species causes malaria. Achieving only one or some of Koch’s postulates show that the microorganism and disease are correlated. However achieving all the postulates creates a strong case that the microorganism in question causes disease.

1. THE Plasmodium SPECIES OCCURS IN EVERY CASE OF MALARIA. (Ross and Woodward 2016)
   This postulate shows that the Plasmodium and malaria are correlated. To achieve this postulate, individuals with malaria can be selected by choosing those who present the symptoms of malaria such as anaemia, nausea, vomiting and fever. Then, a blood smear test can be done to test for the presence of Plasmodium in these individuals. This involves taking a blood sample from the subject, placing it onto a glass slide and adding a stain so that the Plasmodium appears purple when observed under a microscope. A ‘positive blood smear’ refers to a blood smear test where Plasmodium is detected, and is the expected outcome for this postulate.  
   
2. THE Plasmodium SPECIES DOES NOT OCCUR NON-PATHOLOGICALLY. (Ross and Woodward 2016)
   Achieving this postulate shows that the Plasmodium species is necessary for malaria to occur. The steps involved are similar to the first postulate, however healthy individuals are selected instead. This can be done by carefully selecting those who do not present the symptoms of malaria and making sure that individuals with asymptomatic malaria are not selected. Then, a blood smear test can be carried out on these individuals, where a negative blood smear is expected. 
   
3. MALARIA OCCURS WHEN THE Plasmodium SPECIES IS INTRODUCED INTO A HEALTHY ANIMAL MODEL.  (Ross and Woodward 2016)
   This indicates that malaria has occurred in the animal model, such as mice, as a result of the introduction of Plasmodium, hence suggesting that Plasmodium causes malaria. The Plasmodium that is used for this postulate must come from a pure culture that has been created by isolating Plasmodium from an individual with malaria. This is to ensure that malaria occurred in the animal model due to the introduction of Plasmodium, and not because of other factors.
   
4. THE Plasmodium SPECIES CAN BE ISOLATED FROM THE DISEASED ANIMAL MODEL. (Ross and Woodward 2016)
   This postulate ensures that the microorganism survived in the animal model, hence supporting that Plasmodium causes malaria. Plasmodium can be isolated from the diseased animal model by taking a blood sample and isolating any red blood cells that are infected with Plasmodium. 

In addition to Koch’s postulates, there are the MOLECULAR KOCH’S POSTULATES. These show whether a gene of the microorganism enables the microorganism to cause disease. Hence, achieving these postulates can further demonstrate that a Plasmodium species is pathogenic. These postulates involve;  

1. Showing that the gene in question is present in all cases of malaria. 
   
2. Knocking out the gene in question from Plasmodium and introducing the Plasmodium into an animal model. 
   If malaria does not occur, this indicates that the loss of the gene prevented Plasmodium from causing malaria. In turn, this suggests that the gene is necessary for malaria to occur. However, the process of knocking out the gene in question may have interrupted another gene that actually contributes to malaria, whilst the gene that has been knocked out may not actually be involved in malaria at all.  
   
3. Hence, the gene in question needs to be reintroduced back into Plasmodium, and that Plasmodium needs to be introduced into an animal model. 
   If the animal develops malaria, this indicates that the only explanation that malaria did not occur in the previous postulate was because the gene of interest was knocked out. Hence, this further supports the hypothesis that the gene of interest allows Plasmodium to cause malaria in the host. 

Ross LN, Woodward JF, 2016, ‘Koch’s postulates: An Interventionist perspective’, Studies in History and Philosophy of Biological and Biomedical Sciences, 59, pp 25-46, viewed on 1st September 2019, <https://www.ncbi.nlm.nih.gov/pubmed/27315189>