British royal family, variolation used by, 9, 10, 179
British Royal Society, 8–9
Broadly neutralizing antibodies (bnAbs), 178
Bubonic plague, xi–xii, 103, 119
Burnet, Macfarlane, 76–78
Caroline, Princess, 9, 10, 179
Challenge trials, 166
Chicken cholera, 29, 157
Chicken pox, 65
China, 9
bats in, 56–57
bubonic plague in, xi
COVID-19 and, 52, 57, 111, 116, 117, 122–123
SARS and, 52, 56–57
Wuhan, 52, 57, 111, 116, 117, 122–123
Chirality, 27
Chloroquine, 89, 90, 151
Cholera, 25, 26
chicken, 29, 157
Koch, Robert, and, 24, 26
outbreaks and pandemics, 25, 26
sanitation and, 26
Cholera vaccine, 30, 157
Civets, 56
“Clinical trial,” first, 9–10
Cloning, molecular. See Recombinant DNA technology
Community spread, 118
Contact tracing, 115–119
Coronaviruses, 174. See also MERS; SARS; SARS-CoV; SARS-CoV-2
in bats, 55–58
contrasted with other RNA viruses, 54, 59
mutations in, 53–55
nature of, 54
origin and causes, 53
overview, 50, 52
spike proteins and, 54, 174
types of, 52, 53, 105
vaccines against, 178, 184
COVID-19 (coronavirus disease 2019), 58, 67, 68, 113. See also SARS-CoV-2
asymptomatic infections, 98, 113, 116, 118
cytokine storm, 152 (see also Cytokine storm)
immune responses, 99
immunity to, 67–68
symptoms, 6, 45, 58, 98, 116
transmission, 45, 53, 58, 106, 116
treatment, 71, 122, 140, 149–151
COVID-19 pandemic, xiii, 52–53, 58, 64, 103, 111, 113, 116–118. See also specific topics
China and, 52, 57, 111, 116, 117, 122–123
compared with other pandemics, 7
coping with and managing, 116, 121, 149–151 (see also “Weathering the storm”)
social distancing, 117, 119, 121–123, 128–129, 131
economic costs, 123–124, 181–182
epidemiology, 110, 111, 113, 117, 118
mortality rate, 5, 25, 58, 106
in historical context, 37–39
lessons learned and things gained from, 133, 176, 180, 182, 183, 185–187
in Sweden, 128–129
COVID-19 testing, 6, 82, 84, 118
COVID-19 vaccine, 67–68, 162, 177, 183–186
clinical trials, 162, 165, 166
race to a, 33, 173–176
Cowpox, 15
Jenner and, 11–13, 15, 29, 30, 157
smallpox and, 12, 30, 157
vaccination and, 30, 157
variolation and, 11, 12, 157
Culture, microbiological, 23, 24
defined, 23
growing bacteria in, 23
Cytokine blockers, 97, 151–152
Cytokines, 96, 99
innate immunity and, 96–98, 151, 154
T cells and, 93, 96, 99
Cytokine storm, 97, 99–100
inhibiting a, 151–152
Cytotoxic T cells. See Killer T cells
Darwin, Charles, 55, 78
Davis, Mark, 88, 89
Dendritic cells, 73
Depletion theories, 5
Dexamethasone, 150
Diphtheria, 70–71
DNA
overview and nature of, 40–43
proteins and, 42–43, 46–49
DNA genome, 46, 48, 49, 64, 142
DNA polymerase, 41, 50, 142
DNA replication, 41–42, 54, 143
DNA technology, recombinant, 146, 159–162
DNA vaccines, 162, 164
DNA viruses, 45, 46, 142. See also specific viruses
examples of, 64–65
Doherty, Peter C., 87–90, 92
Dunning, Richard, 13, 15
Ebola virus, 105, 140
polymerase, 145
Ebola virus disease, 106
mortality rate, 105, 106
treatment, 139–140, 149, 152
Eisen, Herman, 78
Elion, Gertrude, 142–143, 145
Enders, John, 136, 169, 170
Epidemiological models, 111–115
developing robust, 183
Evolution, 55, 78
Expulsion theory, 3–5
Fever and viral replication, 96
“Flattening the curve,” 119–123, 129
Flu. See Influenza
Food and Drug Administration (FDA), 167, 179
Formaldehyde, 159
Fracastoro, Girolamo, 4
Fuller, Thomas, 5
Genome, viral. See also DNA genome
herpesvirus genome, 64–65
in influenza, 60
mixing (see Recombination)
polymerases and, 142, 143
in RNA viruses, 64 (see also RNA genome)
and viral replication, 138, 142, 143
Genomic information. See also RNA genome
retroviruses and, 48, 49
used to test for viral infection, 49–50
in viruses, 45–46
Genomic sequencing, 49, 137. See also SARS-CoV-2: sequence
Germ theory, 22, 26
Gilead, 149–150
Glycoproteins. See Spike proteins
Good manufacturing practices (GMP), 167
HA (hemagglutinin), 59–61
Hedrick, Steve M., 88, 89
Helper T cells, 155
Hemagglutinin (HA), 59–61
Hepatitis B virus, 150, 160
Hepatitis C virus (Hep C), 145–146
pharmacological treatment, 146, 147, 149, 150
Herd immunity, 125f, 127–128, 127f
acquired by intermittent social distancing, 130–133
defined, 125
portion of population that must be immune to achieve, 125–128
to SARS-Cov-2, 128, 129, 131, 173, 176
through natural infection, 126, 129, 131, 153–154, 173
vaccination and, 18, 126–127, 133, 154
to Zika virus, 128, 174
Heredity, origin of, 40
Herpesvirus, 38, 65, 143
Herpesvirus genome, 64–65
Hitchings, George, 143
HIV (human immunodeficiency virus), 62–64, 135
antibodies against, 81, 82, 177–178
drug treatment, 63, 135, 143, 145, 148, 149
genome, 49
identifying/discovering, 63, 136
mutation and, 62, 64, 177, 178, 184
polymerase and, 142, 143, 145
protease and, 145
replication, 145, 177
SARS-CoV-2 and, 138, 145, 177
T cells and, 136, 138, 177, 178
transmission, 63
HIV proteins, 145, 173, 177, 178
HIV vaccine, 63–64, 173, 174, 178, 184
long pursuit of a, 176–178
HLA-bound peptides, 90, 92
HLA-bound protein fragments, 93, 99, 154, 177
HLA genes, 86–88, 90
HLA proteins, 90, 91f, 92, 99, 154
Hoffmann, Jules, 94, 95
Hong Kong flu. See under Influenza pandemics
Human challenge studies. See Challenge trials
Human Genome Project, 187–188
Human leukocyte antigen. See HLA
Human papillomavirus (HPV) vaccine, 161
Humoralists, 69–71, 96
Humors, 69, 70f
Hunter, John, 11, 12
Hydroxychloroquine, 151
Immunoglobulin A (IgA), 79, 84, 172
Immunoglobulin G (IgG), 84, 140, 172
Immunoglobulin M (IgM), 79, 84
Immunol
ogical memory, 37, 68, 72, 76, 85, 156. See also Memory cells
Immunology. See also specific topics
blood or cells, 68–71
current understanding of, 72
how the infecting virus meets the immune system, 72–74
dawn of the modern era of, 68–71
Infectivity. See Basic reproductive number
Inflammation, 68, 69. See also Cytokine storm
Influenza, 58–61, 64, 108
fatalities from, 60, 106
origin of the term, 2
spike proteins, 59–61
Influenza drugs, 147–148
Influenza genome, 60
Influenza pandemics, xii, 17, 60, 64
1918 flu pandemic, xii, 60, 108, 119–121, 130
1957–1958 influenza pandemic, 61
1968 flu pandemic, 61
2009 swine flu pandemic, 61
Influenza vaccine, 179–180, 184
Innate immunity, 93–98, 154
adaptive immunity and, 72, 93–96, 98, 156, 160
adjuvants and, 160–162
COVID-19 and, 97, 98, 162
cytokines and, 96–98, 151, 154
phagocytes and, 94, 96–98, 154
vaccination and, 156, 162, 163
Inoculation, 11–13, 15. See also Plasma; Variolation
Interferons, 150
cytokines and, 96–98
genes and, 146, 150
SARS-CoV-2 and, 97, 98, 150
Interferon therapy, 146–147, 150
for hepatitis, 146, 147, 150
Isomers, optical, 27
Janeway, Charles, 94, 156
Jenner, Edward, 11–13, 14f, 15
cowpox and, 11–13, 15, 29, 30, 157
Hunter, John, and, 11, 12
life history, 11
smallpox vaccine, 12–13, 15, 157
variolation and, 11–12
Jerne, Niels Kaj, 76, 77
Johnson & Johnson (J&J), 173, 174
Killer T cells, 93, 99, 154–156, 178
Kitasato, Shibasaburo, 70–71
Koch, Robert, 22–26
anthrax and, 22–23
germ theory and, 22, 26
life history, 22
Koch–Pasteur rivalry, 30–32
Koch’s postulates, 24, 28, 30
Kuhn, Thomas, 5
Leukocyte antigen. See HLA
Life cycle of viruses, 47, 137–139, 138f
Lipopolysaccharide (LPS), 95
Lymph, 73
Lymphatic vessels, 73, 74f
Lymph nodes, 79
Maitland, Charles, 9
Mak, Tak, 88, 89
Malaria, 151
March of Dimes, 169–171
Medzhitov, Ruslan, 95
Meister, Joseph, 31
Memory cells, 85, 93, 101, 155, 156, 159. See also B cells; Immunological memory; T cells
Mendel, Gregor, 40
Mercuriale, Girolamo, 4
MERS (Middle East respiratory syndrome), 52, 56, 58, 174
mortality rate, 57, 58, 105, 106
MERS-coronavirus (MERS-CoV), 53, 57–58, 174, 175
Metchnikov, Élie, 68–71, 97
phagocytes and, 68–71, 73, 93, 94, 96–97, 163
Microscope, microorganisms under a, 20–22
Middle East respiratory syndrome. See MERS
Miller, Jacques, 86–87
Moderna, 175
Molecular cloning. See Recombinant DNA technology
Montagu, Mary Wortley, 9
Mortality rate, 104–106. See also under specific viruses
Mutations
of B cells, 78–79
in coronaviruses, 53–55
HIV and, 62, 64, 177, 178, 184
of SARS-CoV-2, 54, 177, 183, 188
SARS-CoV and, 53–55
viral replication and, 148
Mycobacterium tuberculosis, 25. See also Tuberculosis
NA (neuraminidase), 59
Nanoparticles, 163, 164
Neuraminidase (NA), 59
NS5A inhibitors, 147
Nüsslein-Volhard, Christiane, 94–95
Optical isomers, 27
Organ transplantation, 86–87
Pacini, Filippo, 26
Pandemics. See also specific pandemics
future, 188
why RNA viruses cause, 64
Parker, Janet, 16
Pasteur, Louis, 29. See also Koch–Pasteur rivalry
controversies, 32
discovery involving chirality, 26–27
germ theory and, 22
Joseph Meister and, 31
laboratory notebooks, 32
legacy, 33
life history, 26–27, 31–32
optical isomers and, 27
pasteurization and, 27–29
rabies and, 30–31, 35, 157–158
Roux and, 30–31, 157, 158
spontaneous generation theory and, 28
vaccination and, 15, 29–33, 35, 157
Pasteur Institute, 31, 33
Pasteurization, 27–29
Peptides, 89–90, 91f, 92
Phagocytes, 69–71, 73
innate immune system and, 94, 96–98, 154
nanoparticles and, 163
viruses and, 78, 92–94, 98, 154
Plagues, 7
bubonic plague, xi–xii, 103, 119
Plasma, convalescent, 139, 150
Pneumocystis pneumonia, 135
Polio, 167–169, 172–173
Polio outbreaks, 18, 168
1916 New York City polio epidemic, 168
Polio vaccines, 18, 169
Salk, Sabin, and, 169–173, 179
Poliovirus, 136, 167
Polymerase chain reaction (PCR), 50, 51f
Polymerase inhibitors, 142–145, 144f, 147, 149
Polymerases
DNA, 41, 50, 142
HIV and, 142, 143, 145
RNA, 43, 47, 49, 54, 142
viral, 142, 148 (see also Polymerase inhibitors)
Polyproteins, 145
Protease inhibitors, 145
Proteins. See also Spike proteins
amino acids and, 42–43, 49
cytokines and antimicrobial, 96
DNA and, 42–43, 46–49
genetic mutations and, 54
HLA and, 90–93 (see also HLA-bound protein fragments; HLA proteins)
overview and nature of, 42
peptides and, 89–90, 92
RNA and, 43–44, 46–49, 54, 142
T cells and, 92, 99
vaccines and, 154, 155
RNA, 172–173
subunit, 159–162
viruses and, 44–49, 137
Protein synthesis, 43, 44
Public health measures. See also Social distancing
effects on mitigating a spreading epidemic, 115–133
testing, quarantine, and contact tracing, 115–119
“weathering the storm,” 123–130
Quarantine, 115–117
Quinine, 151
R0. See Basic reproductive number
Rabies, 30–31, 35, 157–158
Razi, Bekr Mohammed ibn Zakariya al-, 3
Recombinant DNA technology, 146, 159–162
Recombination, genetic, 55–56
Remdesivir, 149–150
Reproductive number. See Basic reproductive number
Retroviruses, 48, 49, 142. See also HIV
Reverse transcriptase, 48, 142
Ribavirin, 146
RNA
overview and nature of, 43–44
proteins and, 43–44, 46–49, 54, 142
replication, 54, 172
RNA genome, 45–49, 53–54, 60, 64, 142, 146
RNA polymerase, 43, 47, 49, 54, 142
RNA sequences, 51f
of SARS-CoV-2, 50, 52, 54
RNA vaccines, 162–164
RNA viruses, 45–64
examples of, 50, 52–64
replication, 46–48, 142
retroviruses, 48, 4
9, 142 (see also HIV)
why they cause pandemics, 64
Robbins, Frederick, 136, 169
Roosevelt, Franklin Delano, 168–169
Roux, Pierre Paul Émile, 30–31, 157, 158
Sanitation, xii–xiii, 25, 26, 168
SARS (severe acute respiratory syndrome), 84, 116, 137, 139
2002–2004 SARS outbreak, 52, 56, 58, 84, 104, 115, 116, 174
control and eradication, 52, 57
mortality rate, 52, 57, 58, 104–106
SARS-CoV (severe acute respiratory syndrome coronavirus/SARS-CoV-1), 52, 53, 116
ACE2 and, 54
antibodies against, 84
bats and, 56, 57
identification, 52, 137
interferon and, 150
mutations and, 53–55
origin, 53–57
SARS-CoV-2 compared with, 52, 57, 104, 116
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), 50, 52–53, 55, 67, 97. See also COVID-19
ACE2 and, 45, 54, 72–73, 99, 138, 140
antibodies against, 82, 84, 139, 140 (see also COVID-19 testing; Plasma)
bats and, 56–57
herd immunity to, 128, 129, 131, 173, 176
HIV and, 138, 145, 177
interferons and, 97, 98, 150
mutations, 54, 177, 183, 188
polymerase, 145, 149
SARS and, 53, 56, 58, 84
SARS-CoV compared with, 52, 57, 104, 116
sequence, 137, 174, 175 (see also RNA sequences: of SARS-CoV-2)
spike protein, 45, 54, 57, 72, 140–142, 174–176
SEIR models, 112, 130
Severe acute respiratory syndrome. See SARS
Shield, 124
Shi Zhengli (China’s “Bat Woman”), 56–57
Smallpox
cowpox and, 12, 30, 157
history of
from antiquity to early 18th century, 6–11
Jenner’s paradigm shift, 11–13, 14f, 15, 29
eradication of smallpox from the planet, 15–17
variolation, 9–11, 29–30, 157
Smallpox vaccine
Jenner and, 12–13, 15, 157
early opposition to vaccination, 17–18
Snell, George, 86, 87
Social distancing (measures), 123, 128–130
acquiring herd immunity by intermittent, 130–131, 132f, 133
“crushing the curve,” 122–123
“flattening the curve,” 119–123, 129
related to COVID-19, 117, 119, 121–123, 128–129, 131
and a bigger second wave, 121–122, 130
in Sweden, 128–129
weathering the storm and, 123, 124, 128, 130
South Korea, 116–117
Spike proteins, 45
ACE2 and, 45, 54, 72, 138, 140
antibodies and, 77–79, 139, 140, 155, 159, 161, 174, 175, 177
antiviral drugs and, 141–142
B cells and, 77, 79, 88, 98
of coronaviruses, 54, 174
SARS-CoV-2 spike protein, 45, 54, 57, 72, 140–142, 174–176
of hepatitis B virus, 160
of HIV, 138, 177 (see also HIV proteins)
of HPV, 161
of influenza, 59–61
vaccines and, 154, 155, 159–161, 174, 175, 177
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