Greg
Critser

Recently I had the opportunity to ask Paul Ewald, one of the nation's leading evolutionary biologists, about a subject near and dear to his heart: the evolution of a bug, specifically swine flu. As usual, Ewald, a professor of biology at the University of Louisville, was lucid, cogent and memorable.

In his 2002 book, Plague Time: The New Germ Theory of Disease, Ewald set the bio-med community on its head by arguing that most chronic disease is caused by sub-acute levels of pathogenic origin, rather than genes. His thesis has since generated enormous interest and a growing following in numerous fields. Here are his insights:

Greg Critser:What questions AREN’T we asking about this strain that we should be asking?

Paul Ewald: Whenever we are focused on a disease that has been transmitted recently from another species into humans we are dealing with a pathogen that has not adapted to humans. We need to ask how it will evolve by natural selection. Flu experts talk about mutation and reassortment, but these processes generate the variation on which natural selection acts. H5N1 is a bird virus, which has to evolve into a human virus if it is to cause problems for us. The new H1N1 entered humans as a swine virus. Now that it is being transmitted among humans it is evolving into a human virus. The future course of our such pathogens and the diseases they cause depends on which variants predominate.

Greg Critser: Using your knowledge of how virulence evolves, how would you model the trajectory of this flu? Where will it likely end up?

Paul Ewald: I think that the new H1N1 will evolve to the general level that characterizes all type A influenza viruses, with mortality equilibrating to within a range bounded by roughly one death per 1,000 infections and one death per 10,000 infections. I think that we will see equilibration to this level within a few months. I therefore think that this virus will spread globally but that the overall mortality will fall within the range that is associated with nonpandemic flu. I am certain that it will not, as some experts have suggested, cause a second wave that resembles the super-virulent second wave of 1918 influenza, during which death rates were within a range bounded by about 1 death in 50 infections and 1 death per 100 infections. That second wave arose under unique circumstances at and around the Western Front, where transmission could occur easily from extremely sick immobilized people.

We may well see it return in the northern hemisphere winter, with more infections and more deaths than we will see this spring and summer, but this increase will be a result of the higher frequency of infections that occur during winter and not because it will evolve into a super-virulent form. This new flu warrants our concern because so many people may become infected, but not because it will evolve super-virulence.

Greg Critser: Do you have any sense of mutation rates for this type of flu? Are there endogenous “fighter systems” that are underused but might be supported with simpler solutions?

Paul Ewald: The flu generally causes problems when immune defenses are compromised and when the immune systems causes intense damaging responses to particularly severe infections (i.e., cytokine storms). The best endogenous fighter system is an uncompromised immune system that keeps the virus under control without being pushed to a cytokine storm. This means that people need to take care of themselves: avoid stress, get enough sleep, and get balanced nutrition.

Greg Critser: Do you have any sense of Tamiflu and Relenza as possible enablers of persistent chronic infection—in other words, do they fight or abet the kind of low level infectious states you describe?

Paul Ewald: I know of no evidence or plausible logic that would suggest that antivirals would favor persistent infection. Persistence is a difficult for viruses to achieve. Those examples of persistence that are understood involve sophisticated biochemical mechanisms for long term avoidance of the immune system, for example, by hiding out in cells, elevating the replication of those infected cells, and replicating viral DNA along with the cellular DNA. So far as is known, influenza viruses do not have such persistence mechanisms, and cannot acquire them as a result of exposure to antivirals. The main problems with antiviral usage are side effects and evolution of resistance.

 Critser is the author of Fatland, (2003, Houghton) and Generation Rx  (2005, Houghton). His next book is about aging, and will be published by Harmony Random in Jan 2010..