User:Leucippus/Sandbox/SARS-CoV-2's causal mechanisms

Explication of how SARS-CoV-2 causes COVID-19

“”Solve for me that knot, which has entangled my conceptions here.

—Dante, Inferno Cantos X

Any linguistic forms can be explicated. Explication is not concerned with decreeing dogmatic proscriptions on what can be chosen as the object of an explication. Explication is concerned, however, with testing linguistic forms by their success or failure in practical use.

Source 1: "How does SARS-CoV-2 cause COVID-19?" by Nicholas J. Matheson and Paul J. Lehner Limitation: Source is tertiary. Should be used as place to find references. Pros: Information is more accessible. Is a compendium that brings together various sources that either directly or indirectly deal with my topic of interest.

§1. Identification of interesting or useful quotes

1. "Viruses enter cells and initiate infection by binding to their cognate cell surface receptors. The expression and distribution of viral entry receptors therefore regulates their tropism, determining the tissues that are infected and thus disease pathogenesis."

§2. Charitable translation into the clarificandum

Conventions: Let the symbols enclosed within these quotation marks '1′' (viz. the numeral '1' and the ditto mark '′', respectively) signify the clarificandum.

1. 1′. Viruses enter cells---if and only if---they bind to cognate cell surface-receptors. The process of infection begins when a virus binds to a cognate cell surface-receptor. Viruses can enter different cells and different cells have different biological traits; when viruses infect different cells, the infection---the disease pathogenesis---may be different. Therefore the distribution, and expression, of cognate cell surface-receptors affects which cells are infected by viruses.

§3. Clarification of the clarificandum into a clarificatum

Preparatory notes

Language is not a static entity. It evolves. The sentences of our language have manifold uses and meanings, and what's more, these "meanings" and "uses" are not static. They evolve over time. It is a common assumption that we can completely grasp a concept such as 'animal' or 'green' by simply thinking really hard about it in our armchairs. The reality, however, is that concept such as 'animal' or 'green' have complex and subtle uses that cannot be divined a priori. It is only through empirical investigation that we can start to gain an appreciation for the richness of our concepts; we will often need to draw on all of science: from mathematics, to history. Thomas Reid and J.L. Austin appreciated this point fully.

Essential processes for clarification:

1:First we need to collate precise, accurate, and reliable data (n.b., consult "retraction watch", "science integrity", and PubPeer); preferably continuous quantitative data.

2. From this data we can educe phenomena by perception, statistics, and technology.

3. From the phenomena we can deduce evidence.

4. Have the phenomena accurately measure the parameters which explain said phenomena.

5. Our aim is to implement Newton's hypothesis non fingo as much as possible. That means, using the phenomena as much as possible to inter alia---measure, explain and describe---, only then will we resort to deducing hypotheses.

6. Next we deduce hypotheses which predict phenomena and these hypotheses can be experimentally tested and subsequently verified, confirmed, or falsified.

In short we must maximise the connections our theory has to observation, and maximise the quantity of phenomena we have available for further inferences and measurement. Once we have exhausted these activities, we can supplement and enrich them with hypotheses.

Clarification

The word 'viruses', the subject of the first sentence of (1′), is in the plural form of the noun 'virus'. Thus we may interpret (1′) as declaring that more than one virus, viz. at least two viruses,' enter cells iff they bind to cognate cell surface-receptors'---this interpretation is valid based on the grammar of (1′). However, (1′) may alternatively be interpreted as declaring something about 'all viruses'---this alternative construal is more plausible and more concordant with the other sentences that make up the article that (1′) is a part of.

We may clarify (1′) further by ensuring that it is interpreted in the latter sense and not in terms of the former. Only this quantifier: 'all,'---if adjoined to the left of 'viruses', as it occurs in (1′), will ensure that (1′) is interpreted in the latter sense (whilst, simultaneously, preserving the grammar of that sentence i.e. the plural form of 'virus'). Thus:

(i) All viruses enter cells---if and only if---viruses bind to cognate cell surface-receptors.

The phrase 'enter cells' in (1′) may connote various senses and each sense is sensitive to context of use. Here are some of the senses of 'enter':

1. Intransitive, which is split into further senses:

• To go or come into an enclosed or partially enclosed space.
• To become party to an agreement or treaty e.g. a merger between two companies.
• (legal) To become effective; to come into effect.

1. Transitive: which is split into further senses:

• To record (cf. account/audit) something e.g. in a diary or ledge,
• To cause to go, or be received, into something or someplace,
• To type,
• To be fit into, in a court of law, into regular form e.g. to fit into the rules, judgments, or appearance of the court by being being put in a writing into a record.
• Obsolete sense: To initiate or introduce favourably: "This sword but shown to Caesar, with this tidings, / Shall enter me with him." (from Shakespeare's The Tragedie of Anthonie and Cleopatra).

1. Figurative i.e. as 'enter' occurs in metaphors, analogies, and extended analogies.
2. Also there is the poetical sense of 'enter': the particular rhythmic properties e.g. disyllable.

As demonstrated above, 'enter' is an ambitransitive verb---it can function both as a transitive verb and as an intransitive verb. However, the phrase 'enter cells' in (1′) is a transitive verb, and hence, we shall concentrate on the transitive cases. More precisely, in 'enter cells' the subject 'viruses' does some action(s) to cells---"entering", namely. Thus, 'enter cells' is functioning in the causal sense of the verb 'to enter'.

Even so, the phrase 'enter cells' is still unclear. The causal sense of the verb 'enter' functions in disparate ways in evolved ordinary-language:

1: 'I entered my son at college',

2: 'I'm entering my horse in the race',

3: 'The surgeon entered the scalpel into the soft-tissue',

4: 'Water enters the cells across a semi-permeable membrane by osmosis',

5: 'The shuttle entered the stratosphere',

in each of these cases (1-5) "entering" involves different objects and different actions upon those objects. Furthermore, in each case the sentence has subtle ways in which its use will differ depending on what context it is used in i.e. entering your son at different colleges will be a different process---involving different actions, behaviours, norms etc.; and in each case what "entering", precisely involves, is not particularly well-defined (not that this is a problem, mind; vagueness in respect of boundaries is entirely acceptable---mountains don't have precise points at which we separate one from the other, the decision of where these points of demarcation lie is entirely arbitrary), that is, if one is "entering a horse at a race" when does the entering begin-and-end: when the horse's name is registered, or when the horse is in the starting line-up, or when you have betting odds on the horse, etc. Some these sentences are more amenable to precision than other, but it is a matter of degree that separates them, s.h.. 'Viruses enter cells' is a case in point, it relies on scientific terminology and hence relies on a background theory of more well-defined metrics---how viruses "enter" cells may vary in subtle and multiform ways, but we would expect this penchant for the particular to still be reconcilable with empirical generalisations; and the self-correcting capabilities that allow science to adjust for new facts discovered in the course of inquiry (e.g. about the subtle ways in which cellular entry differs).

Moreover, by considering the article which the sentence (i) is embedded in i.e. the sentences which it relates to, and the purpose(s) of the article, we can further elucidate 'enter' as it functions in (i). The article is meant to provide an overview of a complex scientific topic, it is not a monograph; but at the same time, the content is detailed beyond what would be expected as comprehensible to the uninquiring layman. The article was published in Science which describes itself as follows:

"Science is a leading outlet for scientific news, commentary, and cutting-edge research."

This suggests that Science is geared towards the scientific community, and those who are interested in science. And within this cohort, we may reckon that the articles will range from the less-accessible "research papers", to the more accessible "news and commentary articles". The article we are investigating is not a research paper, nor is it a news article, it seems to be somewhere between "commentary articles and research articles"; it is more akin to an overview, or an encyclopaedic entry. We may reckon, then, that the language suitable to such an article is going to be more comprehensible than a research article and in the process less precise. The use of 'enter' in (i) is plainly comprehensible to most, and appropriate for conveying what is happening, but this apparent clarity may be beguiling, if our aim is verisimilitude and explicitness.

The second component of (i) (connected by the biconditional 'iff') viz. 'viruses bind to cognate cell surface-receptors' is more revealing: it provides us with a mechanism "binding" to "cognate cell surface-receptors", which is being claimed as a necessary condition, for viral entry into cells. Hence we may say that 'enter' in (i) consists of, or begins with, "binding to cognate cell surface-receptors"---but what's missing, however, at least in this sentence (i) is the mention of the dynamics required for a viral particle to move from one spatio-temporal location to another (as it would if it enters a cell).
Consulting the other charitable translations---the clarificanda---, may help us obtain these desiderata:

1′. All viruses [enter] cells---if and only if---viruses [bind] to [cognate cell surface-receptors]. The process of infection begins when a virus binds to a cognate cell surface-receptor. Viruses can enter different cells and different cells have different [biological traits]; when viruses infect different cells, the infection---the [disease pathogenesis]---may be different. Therefore[?] the [distribution], and [expression], of cognate cell surface-receptors determines which cells are infected by viruses.

2′. SARS-CoV-2 [co-opts] the peptidase angiotensin-converting enzyme 2 (ACE2)[enzyme-substrate complex; adsoprtion-absoprtion mechanism?] to [enter] cells ---ACE2 is a cognate cell surface receptor for SARS-CoV-2. Thus, as an instance of (1′): The distribution, and expression, of ACE2 receptors determines which cells SARS-CoV-2 infects.

3′. How SARS-CoV-2 [interacts] with ACE2 is critical to determining both [tissue tropism] and [progression] from early SARS-CoV-2 infection to severe COVID-19.

4′. The authors of this paper are arguing that the causal mechanisms and causal processes involved from 1′-3′ ---viz. [cellular mechanisms and cellular processes]---are the most important domain for understanding how SARS-CoV-2 causes COVID-19; and understanding how these mechanisms and processes of COVID-19 can help us engineer solutions that prevent the development of severe disease and reduce mortality.

5′. SARS-CoV-2’s [180kDa] [Spike protein] facilitates cell entry by either: binding to the [amino-terminal region] of ACE2, or [fusing] its viral membrane to the cellular membrane via the carboxyl-terminal region[Aldehyde viz. Carbonyl and OH; chemical level of explanation].

N.b. square brackets signify potential terms for clarification.

We may supplant the transitive verb ‘enter’ with an admixture of transitive verbs and other expedient grammatical tools that denote precise mechanisms that involves motion.

A viral particle obeys Newton's 1st law of motion. Newton's 1st Law of Motion [with 'virus' substituted, as an instance, at the occurrence of 'body']:= "Every [virus] preserves in its state of being at rest or of moving uniformly forward, except insofar as it is compelled to change its state by forces impressed." When scientists investigated SARS-CoV-2’s causal mechanisms they used inter alia existent theory concerning viruses and experimentation involving various observers: humans, microscopes, in order to perceive phenomena. Phenomena are, more precisely, identical with a subclass of our neural intake and our neural intake includes data from our environment. Phenomena represent the neural intake which we are aware of in perception. Phenomena are patterns one can perceive in open-ended bodies of data. Nothing is “given” (cf. The Myth of the Given) to us in perception, we apply our various inferential and perceptual abilities to, what is otherwise, merely chaotic data.

§4. Paraphrasis

In this section we paraphrase the clarificatum into suitable idioms for regimentation into predicate logic and class theory. This involves paraphrase and not translation. Whilst translation has problematic connotations---chiefly the notion of synonymy---, paraphrase does not involve any notion of synonymy, all paraphrasis claims is partial agreement.

Declarative sentences will be purged of any words or phrases that make the sentence's truth value vary. This will be effected by revising or supplanting words and phrases that cause a sentence's truth value to vary due to:

• Speaker,
• Place/Scene,
• Context, and
• Time.

Any mentalistic terms will be eliminated in favour of behaviourist terms and neurological terms (aka. modern externalised-empiricism).