Koch’s postulates, Covid, and misinformation rabbit holes

Opinion: Take a 19th century German scientist, a 21st century disease and add the internet - the result is a dangerous upsurge in Covid-denial nonsense, writes Associate Professor Siouxsie Wiles.

I’ve had quite a few messages from people who believe they have evidence that Covid-19, or more specifically the virus responsible, SARS-CoV-2, doesn’t exist. They even believe they have the paperwork to prove it. And that paperwork is convincing if you don’t know otherwise. It comes in the form of Official Information Act requests to governments, universities, and scientific and academic institutions all around the world. But this is no global coverup. Instead it’s a case of the internet finding the work of a German microbiologist who died over a hundred years ago combined with people sticking rigidly to a specific definition of the word isolation.

Let’s start with that German microbiologist. Robert Koch was born in 1843 and by all accounts was a very clever chap. He trained as a doctor before becoming one of the founders of microbiology as a field of experimental science. Before his death in 1910 he made lots of important contributions. In the 1870s he discovered that anthrax was caused by the bacterium Bacillus anthracis, the first time a specific microbe was linked to a specific disease. He followed that up in 1882 with his discovery that the slow-growing bacterium Mycobacterium tuberculosis was the cause of tuberculosis (TB). Better known back then as consumption, TB had long been thought to be a hereditary disease.

Koch’s postulates, aka how to tell whether a microbe causes disease

Robert Koch is also famous for his “postulates”, the four conditions he and his mentor Jakob Henle postulated had to be met for a microbe to be considered the cause of a disease. It is these postulates that have now been discovered by the internet and (badly) applied to Covid-19. This is how Koch’s postulates were first laid out more than 130 years ago:

  1. The organism must always be present, in every case of the disease.
  2. The organism must be isolated from a host containing the disease and grown in pure culture.
  3. Samples of the organism taken from pure culture must cause the same disease when inoculated into a healthy, susceptible animal in the laboratory.
  4. The organism must be isolated from the inoculated animal and must be identified as the same original organism first isolated from the originally diseased host.

So, in the light of the 21st century how do the postulates hold up? Well, the first one was soon abandoned by Koch himself with the discovery that people could be asymptomatic carriers of the microbes responsible for cholera and typhoid fever. In the years since, we’ve come to understand that many microbes can live in and on people and only cause disease under certain circumstances. We’ve also come to understand that some microbes can set off a chain reaction that leads to disease long after the organism in question has been cleared by the immune system.

The second postulate should really read something like: it would be nice if the organism could be isolated and grown in pure culture. That’s because we don’t even know the conditions under which many microbes grow outside of their host. Take Mycobacterium leprae which causes leprosy. As far as we know, that can only grow in humans, nine-banded armadillos, and a mouse’s footpad. Just because we can’t grow it in pure culture doesn’t mean it isn’t responsible for leprosy. Indeed, using genomic sequencing, we know there are way more microbes than we’ve ever been able to grow in pure culture.

Obviously postulates three and four suffer from the same issue if the microbe can’t be grown in culture. Postulate three would also be better phrased as should cause the same disease when inoculated into a susceptible animal in the laboratory. I say should and specify susceptible because we also now know that some microbes can’t cause disease in a healthy host but can if the host is immune-compromised.  

But wait! What about viruses?

The worst thing about Koch’s postulates is that they were formulated before viruses were known to exist. Viruses aren’t like the bacteria that Koch was busy discovering. Viruses need to take over a host cell to replicate. In other words, they turn cells into virus-producing factories. And depending on what proteins a virus has on its surface, it may only be able to infect very specific cells from certain host species, or a wide range of cells from lots of different species.

That’s why when virologists want to isolate a virus from a sample they’ll take the sample or some part of it and add it to some cells – usually ones that are relatively easy to grow in the lab – and then look to see if the cells die and/or if there are any virus particles released into the liquid nutrient bath the cells are growing in.

In other words, viruses can’t be grown in pure culture as described by Koch’s postulates because they need a cell to grow in. Does that mean viruses don’t cause disease? No.

Bringing Koch’s Postulates into the 20th century

Over 30 years ago, one of the modern-day leaders of microbiology Professor Stanley Falkow reworded Koch’s Postulates to bring them more up to date. Falkow, who died in 2018, was at the forefront of research into how specific genes possessed by particular microbes contribute to their ability to cause disease. In a nutshell his “Molecular Postulates” state that:

  1. The trait under investigation should be associated with pathogenic members of a genus or pathogenic strains of a species. Pathogenic means having the ability to cause disease.
  2. Specific inactivation of the gene(s) associated with the suspected trait should lead to a measurable loss in pathogenicity or virulence in a suitable animal host. In other words, inactivating the gene or genes should mean there is less disease.
  3. Reactivating the gene or genes should restore the ability of the microbe to cause disease in a suitable animal host.

Even with these updated postulates, it’s still not currently possible to satisfy them for many microbes that cause human disease as they rely on the ability to be able to grow and genetically manipulate the microbe in question and have a suitable animal model. That doesn’t mean the postulates aren’t useful, just that microbiologists might not completely rule out an organism or gene being involved in causing disease even if the postulates can’t be fulfilled.

When so-called evidence isn’t worth the paper it’s written on

Back to the evidence being used to prove the virus responsible for Covid-19 doesn’t exist. This is what is being asked of governments, universities, and scientific and academic institutions around the world:

“All records in the possession, custody or control of [name] describing the isolation of a SARS-COV-2 virus, directly from a sample taken from a diseased patient, where the patient sample was not first combined with any other source of genetic material (i.e. monkey kidney cells aka vero cells; lung cells from a cancer patient).”

The copies of the requests I’ve been sent also go on to state:

“Please note that I am using “isolation” in the every-day sense of the word: the act of separating a thing(s) from everything else. I am not requesting records were “isolation of SARS-COV-2” refers instead to: the culturing of something, or the performance of an amplification test (ie a PCR test), or the sequencing of something.”

In other words, the people asking for evidence of the existence of the SARS-CoV-2 virus responsible for Covid-19 are specifically wording their request to rule out obtaining any evidence that the virus exists. As I’ve pointed out, viruses need a host cell to replicate in which is why samples are combined with another “source of genetic material”. This is just biology.

And as for using isolation in the every-day sense of the word, rather than the definition that is relevant to the question being asked? Well, that’s just bloody ridiculous and a clear sign these requests for evidence are not being made in good faith.

And before they pivot to yelling about human exosomes, these aren’t the smoking gun either. Yes, exosomes (more commonly referred to as vesicles) are small particles that can be separated from samples by centrifugation. The important distinction here is that they are bits of our cells that bud off and generally require huge volumes of material to isolate them from. The same processes just can’t be applied to a small sample of cells from someone’s nasal swab.

So regardless of what people believe about “virus theory” or what they think their seemingly vexatious requests for evidence show, Covid-19 continues to cause devastation around the world. The sad thing is, bad faith arguments like these are undermining attempts to bring the pandemic under control. And the consequences of that are deadly.

Associate Professor Siouxsie Wiles is a microbiologist from the Department of Molecular Medicine and Pathology in the Faculty of Medical and Health Sciences' School of Medical Sciences.

This article reflects the opinion of the author and not necessarily the views of the University of Auckland.

Used with permission from The Spinoff, Siouxsie Wiles: Koch’s postulates, Covid, and misinformation rabbit holes, 15 November 2020.

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