Moelling's "Viruses - More Friends Than Foes" (2017).
Oldstone then explains how the immune system works via a combination of
antibodies and T-cells.
He explains the three methods to develop vaccines known at his time:
the one based on a "live" (or better "attenuated") virus
(like Sabin's polio vaccine),
the one based on a "dead" virus
(like Salk's polio vaccine)
and the recombinant method.
He doesn't mention RNA vaccines despite the fact that were already in clinical trials (for cancer) since 2001. BioNTech was founded in 2008, Moderna in 2010. In 2020 they both unveiled the covid vaccines based on RNA technology.
We learn that measles is highly contagious and that smallpox is highly lethal (30% death rate).
Part 2 of the book tells the "success" stories of smallpox, yellow fever, measles and polio.
Oldstone thinks that smallpox came to Europe via the Muslim invasions, and then
European spread it via the trade routes, the Crusades and the long-distance
explorations, the most gruesome case being that of the extermination of Aztec
and Inca population. He retells the story of how smallpox "variolation", already known in the Ottoman Empire, was rediscovered in Britain. This has all been told
before in McNeill's book, and adds details to how
Edward Jenner, a country physician, developed the first smallpox vaccine
in 1796 using the much milder cowpox (indirectly, a "live" attenuated virus).
There are still stocks of variola virus in the USA and in Russia.
Oldstone warns us that smallpox could come back and encourages countries to
vaccinate against smallpox even through the disease is theoretically eradicated.
Yellow fever (an RNA virus) was imported into the Americas by the Atlantic slave trade.
Yellow fever (unlike smallpox) does not spread from person to person by contact: it spreads via mosquito bites.
The ships transported the mosquito Aedes Aegypti, and the slaves transported the virus.
Trading ships transported both to the Mediterranean ports.
It was hard for scientists to explain epidemics of yellow fever because it did seem to spread from person to person.
The mosquito loves tropical climates and found the right climate in Central and
South America, and in US ports during the hot and humid summers.
Oldstone assumes that there was an epidemic of yellow fever in 1648 in Mexico, but that's debated (Spanish colonists were not affected).
Brazil's first recorded outbreak of yellow fever happened in 1685-90.
Europe's first recorded outbreak was in
Spain in 1730, where it killed more than 2,000 people.
After that, there were many in the Americas:
1762 Philadelphia (only 100 died),
1792-99 Santo Domingo,
1793 in Philadelphia (which was the capital of the USA), outbreak that killed about 10% of the city's population, 4000 people,
New York 1795 (730 dead),
1798 Boston, New York and Philadelphia (more than 5,000 dead),
1800 Baltimore (1,200 dead),
1853 New Orleans (8000 dead),
1855 Norfolk (2,000 dead),
1878 Memphis (70% of Caucasians died, 4200, versus 14% of black slaves, 2000 out of 14000) from which it spread to the Mississippi Valley (16,000 dead),
1898 Cuba,
1905 New Orleans (900 dead).
There were fewer outbreaks in Europe: 1804 Italy, 1819-21 Spain, etc.
Eventually, humans understood that the real enemy was the mosquito.
In 1807 John Crawford argued that mosquitoes carried malaria and yellow fever, but he couldn't prove it.
In 1877 Patrick Manson proved that the mosquito transmits disease.
In 1881 the Cuban physician Carlos Finlay argued that yellow fever must be spread by mosquitoes, but again he had no proof.
In 1884 the French physician Alphonse Laveran argued that the mosquito spreads malaria.
When in 1897 British physician Ronald Ross proved that malaria is spread by mosquitoes, and
Giovanni Grassi proved that malaria is spread specifically by the Anopheles mosquito,
Finlay's theory didn't sound so far fetched.
Also in 1897 Robert Koch in Namibia proved that quinine kills the malaria parasite.
In 1900 a US team led by Walter Reed, inspired by Ross' experiment, proved that Finlay was right (Cuba at the time was administered by the USA).
Jesse Lazear was the member of the team who strongly supported the theory: he died of his own experiments.
One man who was immediately convinced was William Gorgas,
the chief sanitary officer of Cuba (at the time controlled by the USA),
who immediately set out to exterminate mosquitoes. He proved the theory right.
A French company had tried to build a canal across Panama in 1881 but had folded in 1889 because the death rate from yellow fever was unsustainable.
In 1904 the USA (after having supported the independence of Panama from Colombia) sent Gorgas to exterminate mosquitoes in Panama and resumed construction of the canal.
The virus itself was not isolated until 1927 (by Adrian Stokes) and a vaccine was available only in 1937 (developed by Max Theiler).
Yellow fever cannot be eradicated because, as shown in 1932 by Fred Soper, the virus has its jungle reservoir in monkeys.
There was an outbreak in 1960-62 in Ethiopia that killed 30,000 people.
In 2015-2016 Angola recorded an outbreak.
The largest outbreak of the last 50 years in the American continent happened in Brazil, originating in the Amazon forest and spreading to urban centers, killing 745 people between 2016 and 2018.
As of 2024, yellow fever is still around in eight African countries: Cameroon, Chad, Congo, DRC, Guinea, Niger, Nigeria, and South Sudan.
In 2023 a handful of cases were recorded in Bolivia and Brazil.
Measles is one of the most contagious diseases. It is due to an RNA virus that is airborne.
It's another disease that decimated entire tribes, like when it spread in the Fiji islands in 1875 killing 20,000 people.
Humans are the natural hosts of measles (like smallpox, and unlike yellow fever, whose natural host is monkeys).
The incubation period can be as long as 12 days during which the victim has no
clue that s/he has been infected. Measles is deadly because it also suppresses
the immune system. In fact, it was the first disease discovered to have this
effect on the immune system. People with measles may die of another disease
because their immune system has been compromised. AIDS is other famous disease
that has this lethal side effect.
In ancient times it was difficult to distinguish measles from smallpox, and so it could be that many "smallpox" epidemics were in reality measles.
Thomas Sydenham's book "Observationes Medicae" (1676) was the first text to
describe measles as a separate disease.
In 1911 John Anderson and Joseph Goldberger discovered that measles was caused by a virus. Developing vaccines for viral infections is more difficult than developing vaccines for bacterial infections (like plague, cholera and typhoid) because bacteria (living beings) can be grown in the lab, while viruses (dead matter) can "live" only when inserted in a living cell.
In 1949 John Enders and others were finally able to grow an animal virus, the polio virus, in a lab.
Their process allowed scientists to grow "live" attenuated versions of a virus,
which in turn
allowed Salk to develop the first polio vaccine in 1952 and
allowed John Enders to develop the first measles vaccine in 1963.
Oldstone briefly mentions the controversy generated in 1998 by a paper
written by the British gastroenterologist Andrew Wakefield that created
panic in parents: Wakefield claimed that the Measles, Mumps, and Rubella (MMR) vaccine was a cause of autism.
The paper was eventually retracted because all scientific studies proved the
opposite, and it was discovered that Wakefield (perhaps for reasons of financial profit) had deliberately cherrypicked the cases that served his case, hiding the ones that proved him wrong. But the damage was done: thousands of parents around the world are still worried that vaccines may cause autism, no matter how many studies refute the argument. Wakefield has made money out of this scandal: in 2016 he directed the anti-vaccination documentary "Vaxxed" which spread a conspiracy theory (endorsed by politicians like Robert Kennedy, a US presidential candidate in 2024).
Polio appears to be a modern disease. Polio epidemics didn't seem to exist
before the 19th century. The first certain description of the disease was written by Michael Underwood in 1790 and the first report of an epidemics was written by
Charles Bell in 1844.
The panic of New York in 1916 became an endemic fear that lasted through the 1950s: it was unpredictable which children would fall down
with polio and who would survive.
Polio is another airborne disease but generally spreads when someone puts in his/her mouth feces of infected people (which happens when people don't wash their hands properly and thus contaminate objects which other people will touch with their hands).
The incubation period can be as long as one month and only 1 in 200 people develop symptoms. It is likely that at the peak every child was infected.
It was a mystery why people were 35 times more likely to catch the disease in August than in April, why children were way more vulnerable than adults, and why more boys than girls were dying and left paralyzed. It is still a mystery today.
In 1909 the Austrian immunologist Karl Landsteiner and Erwin Popper isolated the poliomyelitis virus, but
in 1931 Macfarlane Burnet and Jeam MacNamara discovered that three viruses (not just one) were causing polio, and named them type 1, 2, and 3. This complicated the development of a vaccine because a vaccine had to work for all three types/strains (unlike the vaccines for smallpox and yellow fever).
Polio epidemics escalated in the first half of the 20th century, peaking in the USA in 1952 with 21,000 people paralyzed and 3,000 killed. The majority of victims
were children.
Oldstone explains that it took so many years to get a vaccine for political reasons. The key to funding research for a vaccine was the founding of the National Foundation for Infantile Paralysis (the "March of Dimes") in 1938 by US president Franklin Roosevelt and Basil O'Connor, its director. That foundation collected the money necessary to pay for serious research on polio vaccines.
Jonas Salk developed a polio vaccine in 1952 using an inactivated ("dead") virus.
In 1956 Hilary Koprowski (who had started experimenting with "live" polio viruses in 1947) and Albert Sabin independently developed a
live attenuated vaccine, following in the footsteps of
Pasteur's rabies vaccine, Jenner's smallpox vaccine and mostly
Theiler's yellow-fever vaccine.
In 1960 the USA picked Sabin's vaccine over Salk's and Koprowski's, but in 2000 the USA returned to Salk's inactivated vaccine.
Koprowski has been largely forgotten despite the fact that he was the true pioneer.
Polio was eradicated in the American continent in 1992.
Of the 3 strains of wild poliovirus, type 2 was eradicated in 1999 and wild poliovirus type 3 was eradicated in 2020.
Only a handful of cases have been reported in the 2020s, all of them in Pakistan.
Muslim countries have been the last one to get rid of polio, because of religious superstition (in Pakistan) and because of a conspiracy theory (in Nigeria) that the polio vaccine causes AIDS.
Part 3 deals with the "emergent" threats, like ebola, SARS and AIDS.
The first recorded outbreak of ebola took place in 1976 in Congo Kinshasa: it killed 88% of the infected people. It reemerged in Congo in 1995, killing 77% of those infected. It resurfaced in 2007 in Uganda and in
2014–2016 in West Africa (the largest outbreak yet).
Ebola is not airborne: it spreads via contaminated blood and body fluids.
It is caused by an RNA virus, or, better, by a family of RNA viruses.
In 2002 China gave birth to SARS, caused by a coronavirus, (an RNA virus). Since the first human coronavirus was identified in 1965, scientists have known that coronaviruses can cause diseases, but usually they were mild flu-like illnesses. SARS changed the perception of coronaviruses, and covid in 2019 pushed them to the top of the dangerous viruses.
West Nile (caused by another RNA virus) was first detected in 1937 in Uganda
and became a worldwide sensation when it surfaced in New York in 1999.
It is spread by the Culex Pipiens mosquito, but it appears that less than 1% of those infected get sick.
AIDS is caused by an RNA virus, HIV, that is a retrovirus, i.e. a virus that
can manufacture DNA out of RNA via an enzyme called "reverse transcriptase" and then use that DNA to make RNA inside the infected cell which instructs the hijacked cell to make proteins.
Human retroviruses were "discovered" by Robert Gallo in 1980 when his team discovered HTLV-I.
Luc Montagnier's team discovered another retrovirus in 1983.
In 1984 Gallo's team realized that the cause of AIDS was a retrovirus, HIV.
Gallo also realized that HIV was extremely unstable: every isolated strain was different from the other even when obtained from the same individual but at different times.
Controversy arose when in 1989 a journalist showed that Gallo's HIV was simply
Montagnier's retrovirus:
Montagnier had been first at isolating HIV, but using Gallo's protocol for virus isolation.
In 2006 Beatrice Hahn's group determined that HIV originated in Cameroonian
chimpanzees (Pan troglodytes).
AIDS spreads by sexual transmission and blood transfusion.
Finally, Oldstone deals with influenza, another RNA virus, another airborne disease (whose name was coined by Italians in medieval times for a disease that was "influenced" by the stars, but we don't know if they called "influenza" what we today call "influenza"). The first reliable report of an influenza epidemic is from
1793, written by a Robert Johnson in Philadelphia.
Only in 1933 did scientists identify the cause of human influenza: Wilson Smith, Christopher Andrewes and Patrick Laidlaw discovered the influenza virus.
The famous influenza epidemic is
"Spanish Influenza", which raged during and after World War I. Oldstone thinks that the Germans were ultimately defeated
by the disease just when Russia had collapsed and Germany should have won easily against France. (I am not sure of this because the disease also killed a lot of
French and Italians). The influenza killed more people than World War I did.
Influenza killed most of the US soldiers who died in Europe during World War I.
Influenza killed 500,000 Italians and almost as many Russians.
Countries that had nothing to do with the war suffered a lot, notably in Latin America. It was particularly lethal in the Pacific Ocean.
We don't have the total numbers because the Third World wasn't keeping accurate
records, but certainly in the tens of millions.
For the first time the virus killed young healthy people.
In 2004 Terrence Tumpey was able to reconstruct the original virus, an H1N1 virus that looks like a close relative of bird viruses. In 2014 Michael Worobey published a study that should have proven the avian origin.
The “H” and the “N” in its name refer to proteins (hemagglutinin and neuraminidases) that are found on the envelope of the virus. Many viruses are H1N1,
for example the "Russian flu" of 1977 (which actually originated in China, and
some suspect was the result of a lab leak) and the "swine flu" of 2009 (which
first appeared in Mexico March 2009 and killed an estimated 300,000 people).
The influenza of 1957 (another deadly epidemic) was instead caused by an H2N2 virus.
The influenza of 1968 was caused by an H3N2 virus (first isolated in Hong Kong in July 1968).
The deadly bird flu of 1996 (which luckily didn't spread efficiently from human to human and so mainly affects animals) was caused by a H5N1 virus (first identified in domestic waterfowl in Southern China).
H1N1, H2N2, H3N2 and H5N1 are all Type A viruses, the only type that is known to cause pandemics.
The covid pandemic happened after the publication of the book.
It wasn't a real "pandemic" because "pandemic" means that it affects everybody:
covid didn't affect children, in contrast with influenzas.
RNA viruses like the ones causing ebola, SARS, West Nile, AIDS, influenza and covid can mutate a lot faster than DNA viruses like smallpox. This makes it more difficult to develop vaccines.
Michael Oldstone died in 2023.
