Paying Taxes -- both a virtue and a necessity

 Why pay tax? 

    It is amazing how many people in Britain think taxes are wrong and should be avoided where possible. 

    Nevertheless, I was slightly surprised the other Sunday when the subject cropped up over a pre-prandial pint in the Greatworth Inn. My friend 'the accountant' said he thought that death duties were wrong; that they amounted to double taxation and little different from plain theft. 

    "Maybe", I said, "but still necessary", for I saw an opportunity to lay out my favourite recent aperçu.

    (Apparently it takes a certain sort of intelligence to realise that there are benefits that accrue from taxation: railways, roads, bridges, medicines, the disposal of waste, safety from violence, etc. Some rare citizens even wince at the sight of poverty in the streets. Many can be cajoled into paying taxes by ensuring that all people pay them in some sort of 'fair proportion'. But defining and ensuring fairness is far more easily said than done.  A few years back I crossed swords with a 5th Viscount over the existence of 'altruism' in human populations, which he pooh-poohed . 

    "What about in the paying of taxes?" I had said. 

    "But we do not pay taxes willingly" he objected. 

    "Of course we pay them willingly", I expostulated. "That is to say, a majority of MPs in the house of Commons voted through all the relevant legislation."  The Viscount turned then to other questions, and I was left with the distinct feeling I had routed him.)

    "Have you noticed," I said, returning to my accountant friend and my recent aperçu, "how money continuously flows from poor people to rich people, steadily and inevitably; taxes are needed to return money to the poor so the process can continue." 

    This is a novel idea, for even quite poor people think of  tax as a net loss rather than a net gain, which to them it clearly is. 

    "But, but, but !!! " he protested; "The large incomes of the rich are the result of market forces; it is earned income; the money belongs to the rich by right; they are paid well because they are worth it."

    "All that may be true", I replied; "but it still has to be returned to the poor. It is the accumulation in the hands of the rich that has to be prevented. If the rich spent their income properly, that is to say fully, the inequality might be better tolerated. But they hoard their wealth. And so it must be prised out of their clenched fists." 

    Silence fell.

    "Who is for another beer?"  I offered, for I realised my companions were not up for radically rethinking taxation, and I could see another aperçu coming towards me: "What is a fair tax regime?  It must clearly be a tax regime that prevents the rich from getting richer, and the poor from getting poorer."

    Rather neat, do n't you think, for a Sunday morning?  Death duties are obviously the best way of collecting what must be collected; for only then is it clear how much is involved. (See also: https://occidentis.blogspot.com/2016/09/estate-tax-and-limits-to-wealth.html)

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RNA Vaccines

Currently (12 Nov. 2020), the World Health Organisation (WHO) is aware of 

48 different teams around the world who are working on the production of vaccines against the SARS-Cov2 virus that have already got to the stage of clinical evaluation. The Pfizer/BioNTech/FosunPharma team, known to all since 9th November when it announced a degree of success, is one of these 48. (There are in addition 160 other vaccine-production teams that are in pre-clinical stages of development.)

A number of different vaccine technologies are being tried in the 48 different vaccine-teams that are already at the stage of clinical trials, listed by WHO [1].  I summarise these below. 

Type 1. Inactivated virus (in this case inactivated SARS-Cov2). This is the approach used in the Salk polio vaccine, which used formaldehyde to ‘kill’ the virus. Formaldehyde can modify the shape of proteins, and the antibodies produced may only react with formaldehyde-treated virus. The virus must be really, really, dead, and safety is a perpetual concern.

Type 2. Replicating viral vectors. Thus, the SARS-Cov2 spike protein gene can be inserted into the genome of a mild virus (e.g. the measles virus or adenovirus). These viruses have their own way of getting into cells and replicating, but introduces a SARS-Cov2 antigen, against which the host can raise antibodies. (See [2]) 

Type 3. Non-replicating viral vectors. Adenoviruses often used.These can get into cells but will not spread in the host. Higher doses are therefore needed. (This is the strategy used by the Oxford/Astra Zeneca team.) 

Type 4. DNA vaccines. The mRNA for a viral gene is copied (using reverse transcriptase) into a double-stranded DNA plasmid that grows happily in bacteria. Large quantities of the plasmid are grown up, purified on columns and used as vaccine. Once inside a cell they should direct the synthesis of e.g. Spike protein (amongst several others.)

Type 5. Protein subunit vaccines. These are a more recent development, and becoming popular, as no virus is involved in the manufacture. The gene for a viral protein can be used to produce large quantities of the protein in vitro. However, the isolated and purified protein may not have the right shape to trigger formation of antibodies effective against native virus. 

Type 6. Virus-like Particles (VLPs) can be prepared by growing cultured cells that produce only sufficient of the viral proteins to form a particle, but are not able to reproduce whole virus. If RNA is needed to form a particle, small bits of irrelevant RNA can be added. These particles, purified from cell cultures, can be used as vaccines, and are often more potent antigens than the isolated soluble protein or protein subunits of type 5. Again, no virus is involved in the process of manufacture.

Type 7. RNA vaccines. In this strategy single-stranded mRNA that codes only one viral protein (e.g. the Spike protein) is encapsulated in a Lipid Nano Particle (LNP) some 70-100 nm in diameter [3] (1million nm = 1 mm). Human cells have an inherent tendency to engulf particles of a particular size and attempt to digest them (a hangover, no doubt, from our amoeboid ancestry). The released mRNA directs the synthesis of spike protein (or its Receptor Binding Domain) in the cell. This technology has been developed over the last 20 years for experimentally silencing genes; and since 2012 for producing vaccines against single-strand RNA viruses such as influenza. It was first used in humans in 2017 [4]. The advantage is that an equipped factory can turn to producing a novel vaccine within a week. All it needs is to know the sequence of the mRNA. (This is the strategy use by the Pfizer/ BioNTech/ FosunPharma team, and a team at Imperial College, London.) RNA is far more susceptible to hydrolysis than either protein or DNA (because of the -OH, group missing in 2' desoxyribose). Vaccines are conventionally kept at 5-8ºC, but RNA vaccines must be kept at –78ºC or lower. That is not a problem. A 6 litre dry-ice or liquid nitrogen Dewar, twice the size of a pressure cooker, will hold its temperature for 200 days.

We see that the different vaccine strategies have their own advantages and disadvantages. The RNA technology has the advantage of speed; and relative safety. 

References

[1]    https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines

[2]    https://doi.org/10.1016/j.virol.2014.01.002 

[3]    https://www.liebertpub.com/doi/full/10.1089/nat.2018.0721

[4]    https://pubmed.ncbi.nlm.nih.gov/28457665/

Open letter to the PM

Dear Boris Johnson,

I am by no means your greatest fan, but I thought you ought to know that the R0 number is now (3rd November 2020) below 1. That is to say, your 3-tier system has, to some extent, worked. Though it may well be best to stick with the 4 week lockdown-2, already announced. We still have much to learn about hygiene.

In the attached picture I have plotted the logarithms (base 10) of the daily new cases as reported on https://coronavirus.data.gov.uk. The horizontal axis shows the days of the year (day 279 is 5 Oct,, day 294 is 20 Oct., day 308 is 3 Nov.). 

It is clear that the rising line in blue (data from the first 3 weeks of October) cannot be extended through the most recent data (20 Oct - 3 Nov), shown in red.

The rising blue data show a doubling time of 24 days. The least-squares line of best fit is objective, but is not a close fit because of chance vagaries of the data (R-squared=0.62). The falling red data show a halving time of 200 days. (The line is again the least-squares line of best fit). That is to say, in late May 2021 we would still have 10,000 new cases a day (and c. 70 deaths a day) unless we improve our personal hygiene, (or we have a vaccine).  

So the 4 weeks of lockdown-2 should help. In June and July we had 40 times less virus buzzing around, but most people were foolishly unaware that the R0 number was already above 1. (See: https://occidentis.blogspot.com/2020/09/covid-19-case-data-uk.html ). Personal hygiene deteriorated further in early September. 

Yours sincerely, Ian West

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Ian West
9 Thenford Road, Middleton Cheney,
BANBURY, OX17 2NB,
Tel: 01295 713 889; (Mobile: 07474 572 588)

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