A simile for viral infection
Keith S. Taber
Could an oral Covid-19 treatment be available soon?
There was an item on the BBC radio programme/podcast 'Science in Action' (23rd September 2021) about anti-viral agents being used in response to the COVID-19 pandemic: 'Could an oral Covid-19 treatment be available soon?'
In discussing early trials of a new potential treatment, Molnupiravir 1, Daria Hazuda (Vice President of Infectious Disease and Vaccines at Merck Research Labs and Chief Scientific Officer of MRL Cambridge) made the point that in viral infections the virus may trigger an immune response which is responsible for aspects of the illness, and which may continue even when there is no longer active virus present. As part of her interview comments she said:
"But even after someone is infected, the host actually mounts, for all these [respiratory] viruses, a really dramatic immune and inflammatory response. So it sort of lights a fire. And even when the virus stops replicating, you know that fire continues to burn, and in a lot of cases that's what lands people in the hospital. And so you want to prevent the virus from igniting that fire, that is what really ends up causing a huge amount of damage to the patient. …
the greatest benefit [of the antiviral drug being tested] is in the outpatient setting before that fire gets ignited."
Daria Hazuda being interviewed on 'Science in Action'
A scientific simile
Science communicators, such as teachers, but also scientists and journalists presenting science in the public media, often use techniques to 'make the unfamiliar familiar', to get across abstract or difficult ideas in ways that their audience can relate to.
These techniques can include analogies, metaphors and similes. Here Dr Hazuda used an analogy between the damage to tissue that can occur in disease, and the damage a fire can do. In particular, she was suggesting that the virus may be seen as like something which ignites a fire (such as a match or a spark) but which is not needed to keep the fire going once it had taken hold.
She introduced this idea by suggesting that the virus "sort of lights a fire". This can be considered a simile, which is a figure of speech which is a kind of explicit comparison where one thing is said to be like or similar to another.2 Dr Hazuda did not suggest that the virus actually lights a fire, but rather it has an effect which can be considered somewhat like ('sort of') igniting a fire.
"We didn't start the fire
It was always burning, since the world's been turning
We didn't start the fire
No, we didn't light it, but we tried to fight it"
Billy Joel
Viruses triggering long term disease
The symptoms we experience when ill can be the results of our immune system reacting to illness, rather than the direct effect of the disease causing agent. That does not mean the disease itself would not harm us (infectious agents may be destroying cells which would not be obvious until extensive damage was done), but that in some conditions what we notice – perhaps sneezing, coughing, a raised temperature – is due to the immune response.
The immediate context of the Science in Action interview was the current COVID-19 pandemic caused by infection with the SARS-CoV-2 virus. However, the idea that a viral infection may trigger ('ignite') a longer term immune response (the 'fire') is not new with COVID. The syndrome sometimes known as chronic fatigue syndrome has unknown cause(s), but viruses are among the suspects. Viruses have been suspected as being a possible trigger (if perhaps in combination with other factors) in a range of autoimmune conditions. In autoimmune conditions the mechanisms that usually protect a person from infectious agents such as (some) bacteria and viruses attack and destroy the person's own cells leading to inflammation and potentially serious tissue damage.
People might commonly say that the immune system is 'meant' or 'intended' to protect us from diseases and that it sometimes 'goes wrong' leading to autoimmune disease – but strictly this is not a scientific way of thinking. The immune system has no purpose as such (this would be 'teleological' thinking), but has just evolved in ways such that it has on balance increased fitness.
From that perspective, it might not seem so strange that our immune systems are sometimes insufficient to protect us from harm, and yet can also sometimes be over-sensitive and start doing damage – as that surely is what we might expect if evolution has (through natural selection) led to a system which has tended on the whole to be protective.
The admirable HLA-B27?
"HLA B27 plays an admirable, perhaps outstanding role in the immune response to viruses, however, it is also directly involved in the pathogenesis of the spondyloarthropathies"
Bowness, 2002: 866
My late wife Philippa was diagnosed with a complex autoimmune condition – she was told that she had atypical Wegener's granulomatosis (a disease now usually called Granulomatosis with polyangiitis 2), a form of vasculitis (a disease leading to inflammation in the blood vessels), and that she might have been genetically susceptible to autoimmune diseases because she produced a particular type of human leukocyte antigen, HLA-B27. HLA is an important component of human immune systems, but the precise antigens a person produces varies, depending on their genes (just as we all have blood but people can be assigned into different blood groups). It was also suggested to her that an otherwise minor infection may have acted as a trigger in setting off the autoimmune problems.
Medicine today has some effective agents such as steroids that help 'dampen down' the 'fires' that damage tissues in autoimmune diseases. But these conditions can be very serious. Fifty years ago, most people found to have Wegener's granulomatosis were dead from that damage within a year of their diagnosis.
HLA-B27 is only found in a minority of people in most populations and is associated with a higher prevalence of certain immune conditions such as ankylosing spondylitis (an inflammatory condition especially affecting the spine), inflammatory bowel disease, and some forms of arthritis. It might seem odd that evolution has not led to the elimination of HGLA-B27 if it is associated with serious medical conditions. Yet, again, it may be that something which can make people prone to some conditions may also be better at protecting them from others.
People with HLA-B27 may be better at mounting an effective immune response to some viral infections (the fire is more readily ignited, we might say) and this might be enough of an advantage to balance its unfortunate role in autoimmune conditions. Over human history, HLA-B27 might have protected a great many people from dangerous infections, if also being responsible for a smaller number becoming very ill.
"HLA-B27 appears to excel at its natural function of binding and presenting viral peptide epitopes to cytotoxic T cells. We have suggested that HLA-B27 may, however, act as a 'double-edged sword'. Thus, certain features of its peptide binding ability or cell biology (perhaps those favouring excellent antiviral responses) might also lead to autoimmunity."
McMichael & Bowness, 2002: S157
That is, what makes this immune component so good at attacking certain viruses (as if the immune system had been doused in petrol so that the slightest spark might initiate a response) may also be responsible for its association with autoimmune diseases. HLA-B27 may (metaphorically) be the can of petrol that means that a viral spark starts not just a fire, but a conflagration.
Read about science in public discourse and the media
Read about making the unfamiliar familiar
Read about teleological explanations
Work cited:
Bowness, P. (2002). HLA B27 in health and disease: a double‐edged sword? Rheumatology, 41(8), 857-868. doi:10.1093/rheumatology/41.8.857
McMichael, A., & Bowness, P. (2002). HLA-B27: natural function and pathogenic role in spondyloarthritis. Arthritis research, 4 Suppl 3(Suppl 3), S153-S158. doi:10.1186/ar571
Footnotes:
1: "the first oral, direct-acting antiviral shown to be highly effective at reducing nasopharyngeal SARS-CoV-2 infectious virus" according to a preprint reported at medRχiv). A preprint is a paper written to report scientific research but NOT yet tested through peer review and formally published, and so treated as reporting more provisional and uncertain findings than a peer-reviewed paper.
2 By comparison, a metaphor may be considered an implicit comparison presented as if an identity: e.g., the nucleus is the brain of the cell.
2. The disease was named after the German physician Friedrich Wegener who described the condition. After Wegener was identified as a Nazi and likely war criminal (suspected, but not convicted) it was decided to rename the disease.