by Vincent Racaniello on 14 August 2009
When the 2009 H1N1 pandemic influenza virus emerged earlier this year, I began re-reading John Barry’s The Great Influenza. I came across the sentences that I had underlined during my first read identifying errors in basic virology. Because this is a very popular book, it’s important to identify the mistakes and correct them.
Barry is not a virologist, or any type of scientist. He’s a historian who happens to have written on influenza. This does not excuse the virological errors in his book; he should have had a virologist fact-check the manuscript before publication.
Page citations refer to the Penguin Books paperbound version.
When a virus successfully invades a cell, it inserts its own genes into the cell’s genome, and the viral genes seize control from the cell’s own genes. [page 100]
This sentence implies that the reproductive cycle of every virus includes integration of the genome into that of the host. Barry’s statement is incorrect; only genomes of certain viruses (e.g. retroviruses) are introduced into the host DNA.
Soon a pit forms in the cell membrane beneath the virus, and the virus slips through the pit to enter entirely within the cell… [page 103]
Only some viruses enter the cell from the ‘pit’ formed at the plasma membrane. In many cases the ‘pit’ eventually becomes a vesicle known as an endosome which moves deep into the cytoplasm. Influenza viruses enter cells from endosomes.
If for some reason the influenza virus cannot penetrate the cell membrane, it can detach itself and then bind to another cell that it can penetrate. Few other viruses can do this. [page 104]
I presume Barry is referring to the ability of influenza NA to remove sialic acids from the cell surface, thereby liberating surface-bound virions. Other viruses have this ability. Viruses that do not possess a neuraminidase probably have other ways to leave the cell surface, such as a weak virus-receptor interaction.
The following description concerns the entry of influenza virus into cells:
Inside this vesicle, this bubble, shape and form shift and create new possibilities as the hemagglutinin faces a more acidic environment. This acidity makes it cleave in two and refold itself into an entirely different shape. [page 104]
Cleavage of the HA does not occur during endosomal entry. Whether or not the viral HA is cleaved (which is required for infectivity) is determined during assembly of the virus particle.
In the following sentence, Barry seems intent on making a retrovirus out of influenza virus:
Soon the genes of the virus spill into the cell, then penetrate to the cell nucleus, insert themselves into the cell’s genome, displace some of the cell’s own genes, and begin issuing orders. [page 104]
The influenza virus genome does not integrate into the DNA of the host cell, as noted above.
The neuraminidase guarantees that new viruses can escape to invade other cells. Again, few viruses do anything similar. [page 104]
Members of other virus families do have neuraminidases which probably serve similar functions during infection as the influenza NA. It’s not correct to write that ‘few’ viruses do anything similar.
Antibodies, for example, carry thousands of receptors on their surface to recognize and bind to a target antigen. [page 108]
A single antibody does not have the ability to bind thousands of antigens; only one. Collectively, antibodies can recognize thousands of epitopes.
Dendritic cells attack bacteria and viruses indiscriminately, engulf them, then “process” their antigens and “present” those antigens – in effect they chop up an invading microorganism into pieces and display the antigens like a trophy flag. [page 108]
Dendritic cells don’t engulf viruses and bacteria – they take up extracellular proteins by endocytosis, then display them to lymphocytes. Perhaps Barry is thinking of phagocytic cells such as macrophages.
But of all parts of the influenza virus that mutate, the hemagglutinin and neuraminidase mutate the fastest. [page 109]
The mutation rate of all influenza virus RNA segments is similar. What Barry means is that the HA and NA proteins vary more than do other viral proteins. This is because the HA and NA are structurally plastic and can accommodate amino acid substitutions. Changes in the protein are not mutations; this term refers specifically to nucleic acid.
When an organism of weak pathogenicity passes from living animal to living animal, it reproduces more proficiently, growing and spreading more efficiently. This often increases virulence. [page 177]
These conclusions simply are not correct. I discussed this issue previously.
Initially Ebola has extremely high mortality rates, but after it goes through several generations of human passages, it becomes far milder and not particularly threatening. [page 177]
One of the problems with The Great Influenza is that statements such as this one are not supported by literature references. There has been so little person to person spread of ebolavirus that this conclusion cannot be made.
The following statements that implies that there were multiple waves of influenza in 1918 accompanied by mutation to higher and then lower virulence:
All over the world, the virus was adapting to humans, achieving maximum efficiency. And all over the world, the virus was turning lethal. [page 193]
Even when the virus mutated toward mildness, it still killed efficiently. [page 363]
At first those processes had made the virus more lethal. Whether it first jumped from an animal host to man in Kansas or in some other place, as it passed from person to person it adapted to its new host, became increasingly efficient in its ability to infect, and changed from the virus that caused a generally mild first wave of the disease in the spring of 1918 to the lethal and explosive killer of the second wave in the fall. [page 370]
As time went on, it became less lethal. [page 371]
But it mutated enough, its antigens drifted enough, to rekindle the epidemic. [page 373]
It continued to attack, but with far less virulence, partly because the virus mutated further toward its mean, toward the behavior of most influenza viruses. 
As I’ve written before, we have no evidence for an increase or decrease of the 1918 virus with time, because there are no virus isolates other than one reconstructed from November 1918. All these statements are therefore without any proof and remain highly speculative.
It’s not my intent to severely criticize the book – it’s a compelling description of a very serious pandemic. I simply want to ensure that everyone understands the scientific underpinnings of the outbreak. When authors write about science for a general audience, they have an obligation to get the science right.