COVID-19 E-Book

Hugh Pennington

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 163

Veröffentlichungsjahr: 2022

Beschreibung

Within days of the first reports of patients suffering from a mysterious pneumonia in Wuhan, scientists in China had produced a complete genetic sequence of the virus and confirmed that it was a novel SARS-like coronavirus. The genetic sequence was deposited in a public database, making the genetic code available to scientists anywhere in the world. The result was that weeks before the WHO declared the outbreak a global public health emergency and months before COVID-19 was formally designated a pandemic, virologists around the world were already studying the protein spikes on the virus and designing vaccines, which were developed much more quickly, and turned out to be much more effective, than even the most optimistic had predicted. All of this was possible because a biological revolution had taken place a decade earlier: the world had moved into the postgenomic era. In this book, the distinguished microbiologist Hugh Pennington argues that COVID-19 is the first 'postgenomic pandemic' - that is, the first pandemic to sweep the world after the postgenomic era was initiated in 2008. Pennington explains the science behind this crucial development and shows how it has revolutionized our ways of understanding and dealing with pandemics, including the pandemic that brought our world to its knees.

Leseprobe

CONTENTS

Cover

Title Page

Copyright

Foreword

Notes

1 The Postgenomic Age: Its Antecedents

Notes

2 Coronaviruses: The Beginning

SARS

MERS

Notes

3 COVID-19: The Disease

Notes

4 Origins: December 2019–January 2020

Notes

5 Fangcangs and Nightingales: February–April 2020

Notes

6 Test Test Test! March 2020

Notes

7 The Epidemiologic Transition: Setting the Scene for COVID-19

Notes

8 Outbreaks: Learning in Real Time

Notes

9 Whole Genome Sequencing

Notes

10 Variants

Notes

11 Vaccines

Notes

12 Pandemics

Notes

13 The Future

Notes

End User License Agreement

Guide

Cover

Table of Contents

Title Page

Copyright

Foreword

Begin Reading

End User License Agreement

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COVID-19: The Postgenomic Pandemic

Hugh Pennington

polity

Copyright © Hugh Pennington 2022

The right of Hugh Pennington to be identified as Author of this Work has been asserted in accordance with the UK Copyright, Designs and Patents Act 1988.

First published in 2022 by Polity Press

Polity Press65 Bridge StreetCambridge CB2 1UR, UK

Polity Press111 River StreetHoboken, NJ 07030, USA

All rights reserved. Except for the quotation of short passages for the purpose of criticism and review, no part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the publisher.

ISBN-13: 978-1-5095-5216-0

A catalogue record for this book is available from the British Library.

Library of Congress Control Number: 2022933625

The publisher has used its best endeavours to ensure that the URLs for external websites referred to in this book are correct and active at the time of going to press. However, the publisher has no responsibility for the websites and can make no guarantee that a site will remain live or that the content is or will remain appropriate.

Every effort has been made to trace all copyright holders, but if any have been overlooked the publisher will be pleased to include any necessary credits in any subsequent reprint or edition.

For further information on Polity, visit our website:politybooks.com

Foreword

A virus has been described as an ‘astonishingly efficient and beautiful product of nature’ because it is so economical in its genetic information, because it attaches efficiently to host cells, because it effectively directs the manufacture of new virus components and genomes once inside, and because it is stable in the environment but still speedily disgorges its internal components into host cells after contact.1 Inside each SARS-CoV-2 virus, the one that causes COVID-19, is a long molecule made of RNA, its genome. It is surrounded by proteins which enable it to get into the cells lining our noses, throats and lungs, and grow in them. Postgenomics is a convenient term to describe the scientific study in real time of the sequence of the building blocks of that molecule, and the use of that information to detect it, to follow its evolution, to exploit its differences as a fingerprinting tool to track the spread of the virus, and to use it to make vaccines and search for antiviral drugs. The chapters that follow describe the science enabling these endeavours. They are written for the non-scientist.

History explains how we got to where we are, and so chapter 1 describes the development of postgenomics since Watson and Crick and DNA in the 1950s. Chapter 2 describes coronaviruses and their discovery, first as common cold viruses and then as very nasty causes of pneumonia; SARS (originally from bats) and MERS (from camels). Chapter 3 is about COVID-19 as an acute disease, its treatments and its chronic complications. The next three chapters describe early events in the pandemic as they happened, starting in chapter 4 with the possible origins of the virus at the end of 2019, favouring a natural rather than a man-made birth; then, in chapter 5, events in February and March 2020, focusing on a comparison of the English Nightingale Hospitals with their Chinese precursors, Fangcang shelter hospitals; and going on, in chapter 6, to the exhortation in March to test, test, test and the big postgenomic spin-off, polymerase chain reaction (PCR). SARS-CoV-2 is not only modern as a new human pathogen, but particularly deadly because worldwide modernity means that we are living longer and getting fatter, the two most important risk factors for lethality, as described in chapter 7. Local outbreaks give vitally important information about factors that help the virus to spread and have driven control policies, and are covered in chapter 8. The benefits that have come from the method that characterizes the postgenomic era, rapid genome sequencing, are considered in chapter 9 and, with others largely dependent on it, the detection and effects of variants, in chapter 10, and vaccines, in chapter 11. Previous pregenomic pandemics are considered in chapter 12; they put COVID-19 into context and lay the historical foundations for the final chapter. There is one Sam Goldwyn quote I use a lot: ‘Making predictions is difficult, particularly about the future.’ So read its prognostications about what might happen in years to come with scepticism; but do not doubt the importance of luck.

This book is about science. No comment is made about the response of national leaders to the pandemic, or how different nations have coped with it differently, despite it spreading on the air in the same way everywhere, and no comment is made about the impact of that endemic condition, banal nationalism.2 Social media is avoided like the plague. Most tweets have R numbers many orders of magnitude greater than the fastest-spreading microbes.

No account is free of bias. This one is evidence-based. It relies on scientific papers. It is biased because only a few have been chosen for emphasis out of the vast number that have been published; within the first 10 months of the pandemic, more than 125,000 had been written;3 and biased because it is an account written by a molecular virologist4 who has researched virus virulence and virus variants, handled smallpox virus, reverted to bacteriology and investigated E. coli O157, a new pathogen that spread worldwide late in the twentieth century, and a scientist who has long held a positive view about the correctness of John Stuart Mill’s essay on Nature,5 one that COVID-19 has abundantly justified: Nature kills and tortures ‘with the most supercilious disregard both of mercy and of justice’, and the precept that man ought to follow nature is irrational ‘because all human action whatever, consists in altering, and all useful action in improving, the spontaneous course of nature’.

Notes

1.

R. Dulbecco, ‘Basic mechanisms in the biology of animal viruses’,

Cold Spring Harbor Symposia on Quantitative Biology

, XXVII (1962): 519–25.

2.

Michael Billig,

Banal Nationalism

(London: Sage, 1995).

3.

Nicholas Fraser et al., ‘The evolving role of preprints in the dissemination of COVID-19 research and their impact on the science communication landscape’,

PLoS Biology

, 19 (2021): e3000959.

4.

T.H. Pennington and D.A. Ritchie,

Molecular Virology

(London: Chapman and Hall, 1975).

5.

John Stuart Mill,

Nature, The Utility of Religion, and Theism

, 2nd edn (London: Longmans, Green, Reader, and Dyer, 1874).

1The Postgenomic Age: Its Antecedents

We are now in the Postgenomic Age,1 the period that started with the publication of the draft sequence of the human genome in 2000, and has since been characterized by revolutionary technical developments that make it possible for biological research to use whole genome sequencing technologies routinely in real time and draw extensively on the genomic knowledge so generated. COVID-19 is postgenomic because these approaches led to the discovery of its cause, the brand-new virus SARS-CoV-2, the development of the test which dominates the diagnosis of the disease in life, and in death, and the availability of methods to characterize the virus genome in precise detail, enabling the detection of variants in real time and the identification of local, national and international routes of spread, with all these things happening at unprecedented speed. A handful of pneumonia cases were diagnosed in Wuhan in December 2019. Deep lung samples were taken from three of them on 30 December. Exhaustive diagnostic testing showed that the illnesses were not caused by any well-known viruses or bacteria. Application of a central postgenomic method, ultrarapid genome sequencing (often called next generation sequencing), identified the cause as a new virus on 7 January. The genome sequence was published internationally on 10 January, test kits designed using the sequence became available the next day,2 and vaccine researchers had designed and made their first candidate antigens within a week.

Lots of interesting people have made the discoveries and invented the techniques that have made the postgenomic science that underpins the way we recognize, record, research, respond to and resist COVID-19. Sydney Brenner was one. Son of a Lithuanian cobbler who, in 1910, had emigrated to South Africa and who spoke Russian, Yiddish, English, Afrikaans and Zulu but never learned to read or write, Brenner became a giant of molecular biology (awarded the Nobel Prize in 2002). He shared an office with Francis Crick for 20 years. He played a key role, with the electron microscopist Bob Horne,3 in developing negative staining, the electron microscope technique that was used to discover coronaviruses.

Brenner divided biology into epochs. BC was ‘before cloning’. AD was ‘after DNA’. Before it, everything seemed hopeless. After it, thought could be given to trying to sequence genes to get answers to the question ‘How do they fit into the broader picture?’

AD developed into the genomic era. This formally began in 1977, when Frederick Sanger in Cambridge (Nobel Prizes for Chemistry, 1958 and 1980) published the genome sequence of the very small bacterial virus, fX174. It has a DNA genome less than a fifth of the size of SARS-CoV-2. Sequencing this single tiny genome in the mid-1970s took many months. Technical progress in this area continued to be very slow. Sequencing the human genome was first proposed in 1984. The Human Genome Project (HGP) started in 1990. It took 23 years and cost $2.7 billion. Its main results were announced 11 days before the fiftieth anniversary of the publication of Watson and Crick’s description of the DNA double helix. The initial sponsor of the HGP was the US Department of Energy, based at the Oak Ridge National Laboratory in Tennessee, which had been established in the early 1940s to make enriched uranium as part of the Manhattan Project, the place where Teflon came into its own to protect components from uranium hexafluoride, the viciously corrosive gas used in the half-mile-long plant that separated the uranium-235 isotope (used in the Little Boy Hiroshima bomb on 6 August 1945) from U-238. Proponents put the HGP into the same category as the giant accelerators used in nuclear physics.4 It was Big Science. The first microbial Big Science exercise was the E. coli sequencing project, finished in 1997. It took 6 years and involved 259 scientists. Alvin Weinberg, the director of Oak Ridge, compared Big Science to Notre Dame and the Egyptian pyramids as well as to space rockets and experimental nuclear reactors, and was concerned that while it was necessary, it might eventually turn out to be a pathological contagion because its spread could damage Little Science.5 For biology, he needn’t have worried. Quick and cheap methods were developed in the 1960s for comparing bits of genomes (but not whole ones, yet) that did not use complicated equipment or need large teams of technicians. The methods used electrophoresis, in which nucleic acid molecules were separated in porous gels by passing an electric current across a slab of the gel.

Electrophoresis was invented by Arne Tiselius (Nobel Prize for Chemistry, 1948) in Uppsala. His first apparatus was unveiled in 1937. It was massive – 20 feet long and 5 feet high – very expensive and needed a dedicated operator. It was also very slow, had very poor resolving power and could only run one sample at a time. Its successors are more than ten times faster, use bench-top equipment that can run many samples simultaneously with high resolution, cost a hundred times less, and can deliver top-quality results by anyone after a few hours of training. This technical improvement was paralleled by another one that also began in Uppsala. Tiselius worked in Theodor Svedberg’s laboratory. In 1925 Svedberg (Nobel Prize for Chemistry, 1926) unveiled his ultracentrifuge, which generated massive g forces big enough to move big molecules in a controlled way. It occupied two rooms, was driven by an oil turbine, needed a hydrogen supply and vacuum pumps, and, in the words of a US biochemist, Professor Dean Fraser, ‘had to be run behind 3-foot-thick walls of reinforced concrete. The scientists who operated them were considered slightly insane. Centrifuges required constant attention … explosions were to be expected at fairly regular intervals. The Spinco preparative centrifuge, for contrast, is about the size of a washing machine, and anyone can learn to run it in 10 minutes.’ I cut my virological teeth on a Spinco in the 1960s.

Genomics would not have been possible without electrophoresis. However, ordinary DNA molecules, even bacterial ones, are too big to be analysed by it. The discovery of restriction enzymes (Werner Arber, Dan Nathans and Hamilton Smith, Nobel Prizes for Physiology or Medicine, 1978) was a key development. Bacteria make them for defence against virus infections. They recognize the virus DNA as it enters the bacterial cell as foreign, and cut it, making it non-infectious. The cuts are not random but are made at particular DNA sequences along the molecule, so the cutting generates DNA fragments whose size depends on the DNA sequence. They are small enough to be separated in an electrophoresis gel, giving a pattern of bands like a bar code. Fragments with a particular sequence can be detected by hybridizing them with DNA complementary to them labelled with radioactivity. Called Southern blotting, after Ed Southern, its inventor, the electrophoresed DNA fragments are blotted onto a nylon membrane and then treated with the radioactive complementary DNA. Application of an X-ray film to the membrane reveals the bands of interest. The power of this method was dramatically and publicly demonstrated for the first time when it was used by Alec Jeffreys in 1986 during the investigation of two rapes and murders in the English Midlands.

In 2007–8 there was a revolution. Next generation sequencing (NGS), a catch-all term used to define a cluster of technologies, came in. The Postgenomic Age took off. Whole genome sequencing (WGS) of viruses changed overnight from projects that took years, to routine activities that took less than a day per virus, because the speed and cost of sequencing DNA and RNA molecules and genomes had dropped dramatically, massively outpacing Moore’s Law (that the number of components on a microprocessor chip doubles every two years, an annual compound growth rate of 35 per cent).6 The most telling example of this revolution is its impact on the sequencing of the human genome; today, a human genome can be sequenced in 24 hours at a cost of less than $1,000.

An excellent example of a next generation sequencing technique is nanopore sequencing. It was one of the methods used to discover SARS-Cov-2 in early January 2020 and has been used to sequence many thousands of its genomes since, probably about a quarter of those analysed worldwide. By the application of a small voltage, nucleic acids are encouraged to pass through tiny holes in a membrane made of genetically engineered naturally occurring molecules that make pores spontaneously. As the genome moves through the pore, an electric signal is generated showing how much current is running through it. Different nucleotides (the genome building blocks) give different signals which are decoded using special software, so reading the genome sequence.

Kary Mullis is another very interesting person whose scientific contribution has also been central to the postgenomic COVID-19 story. In 1993 he was awarded the Nobel Prize for inventing the polymerase chain reaction (PCR) when working at the Cetus Corporation, a biotechnology company in San Francisco.7 The science journalist Nicholas Wade wrote in The New York Times in 1993 that biology now had two epochs, before and after PCR. Mullis was a badly behaved biochemist. He liked LSD. His private life was complicated. His Nobel Lecture describes the day he set up his first successful PCR with Fred, his technician. ‘As he had learned all the biochemistry he knew directly from me, he wasn’t certain whether or not to believe me when I informed him that we had just changed the rules in molecular biology. “Okay, Doc, if you say so”.’ Mullis became notorious after leaving Cetus because of his scepticism that AIDS was caused by HIV. He was wrong about that, but he was right about PCR.

PCR is a simple method for making with great speed many millions of copies of a DNA molecule. It works for SARS-Cov-2 but only after its RNA genome has first been converted into DNA using the enzyme reverse transcriptase, discovered by Howard Temin and David Baltimore (Nobel Prizes, 1975). Heating and cooling are essential steps in a PCR reaction. Using a heat-resistant enzyme to do the copying makes it much easier and much faster. Taq polymerase from the bacterium Thermus aquaticus is used. It came from hot springs in the Yellowstone Park, and grows best at 65–70°C. It is said that early in the COVID-19 pandemic, demand was so great that supplies of taq polymerase began to run short worldwide. PCR is the commonly used appellation for the test. Its full name is Rt-qPCR, Rt standing for reverse transcriptase, and q for quantitation, because the test result gives the amount of DNA it has found, an accurate measure of the amount of RNA on the nose/throat swab.