In Tuesday’s comments, Kriss brought up Paul Ewald, father of the “Ewald hypothesis.” (Also brought up by Dennis Mangan here.) Ewald did some of his work in collaboration with Gregory Cochran, who may be familiar to many for his appearances on blogs (notably at Gene Expression) and for his recent book The 10,000-Year Explosion.

In a 1999 Atlantic article, “A New Germ Theory,” Judith Hooper summarizes Ewald’s hypothesis:

Darwinian laws have led Ewald to a new theory: that diseases we have long ascribed to genetic or environmental factors — including some forms of heart disease, cancer, and mental illness — are in many cases actually caused by infections.

Regular readers won’t be surprised to hear that we wholeheartedly endorse the Ewald hypothesis. We believe that nearly all diseases are caused by infections and bad diet. Malnourishing, toxin-rich diets impair immune function and create vulnerability to infectious disease.

The Ewald Hypothesis

Ewald’s reasoning goes as follows. Quotations are from the Atlantic essay.

First, genetic causes of disease are unlikely. Any gene that led to impaired functioning of the human body would be selected against and removed from the genome. Therefore, genetic diseases should have the abundance of random mutations – about 1 in 100,000 people:

As noted, the background mutation rate — the ratate which a gene spontaneously mutates — is typically about one in 50,000 to one in 100,000. Not surprisingly, genetic diseases that are severely fitness-impairing (for example, achondroplastic dwarfism) tend to have roughly the same odds, depending on the gene.

Diseases that are fitness-impairing and reach higher prevalence – and this includes nearly all major diseases – must have a cause other than genetic mutations.

Germs, on the other hand, are plausible candidates as causes for disease. Germs can benefit from doing us harm. At a minimum, they would like to modify human functioning in order to make us better hosts for themselves — by suppressing immune function, for instance. Also, they wish to induce behaviors that help them spread to new hosts – like sneezing, coughing, diarrhea, or sexual promiscuity.

Germs evolve quickly. Gene exchange, and lack of error checking during gene replication, modifies genomes quickly. Short reproductive time scales – on the order of 20 minutes – mean that helpful mutations proliferate rapidly. Big evolutionary changes can occur in a few weeks:

“The time scale is so much shorter and the selective pressures so much more intense [in microbes]. You can get evolutionary change in disease organisms in months or weeks.”

This means that germs quickly optimize their disease characteristics through natural selection. For example, virulence, or the severity of the disease that a pathogen causes, is rapidly optimized.

One factor determining virulence is how easily the organism can spread to a new host. If the organism can spread easily, there’s little cost to harming the current host, and microbes produce severe disease. If it’s hard to spread, on the other hand, organisms will be mild and peaceable toward their hosts. It pays to keep their hosts alive and healthy.

Ewald and his students collected empirical data supporting their explanation for virulence:

The dots on Saunders’s graphs made it plain that cholera strains are virulent in Guatemala, where the water is bad, and mild in Chile, where water quality is good. “The Chilean data show how quickly it can become mild in response to different selective pressures,” Ewald explained…. Strains of the cholera agent isolated from Texas and Louisiana produce such small amounts of toxin that almost no one who is infected with them will come down with cholera.

In the last few decades, evidence has only grown for the infectious origins of most diseases. In 1999, over 80% of serious diseases were known to be caused by pathogens:

Of the top forty fitness-antagonistic diseases on the list, thirty-three are known to be directly infectious and three are indirectly caused by infection; Cochran believes that the others will turn out to be infectious too. The most fitness-antagonistic diseases must be infectious, not genetic, Ewald and Cochran reason, because otherwise their frequency would have sunk to the level of random mutations.

If this analysis were repeated today, the percentage would be still closer to 100%. More cancers are now known to be caused by viruses, and the links between microbes and cardiovascular disease, dementia, and multiple sclerosis are stronger than ever.

I think Ewald and Cochran are correct in asserting that mental and neurological illnesses are especially likely to be infectious in origin. These illnesses tend to have a big impact on number of descendants, supporting the evolutionary argument for an infectious origin. And, due to their dependence on glucose, neurons are unusually susceptible to infections.

Schizophrenia is a good example of a disease that must be infectious in origin:

From the fitness perspective, schizophrenia is a catastrophe. It is estimated that male schizophrenics have roughly half as many offspring as the general population has. Female schizophrenics have roughly 75 percent as many. Schizophrenia should therefore approach the level of a random mutation after many generations.

Ewald and Cochran suggest we need a “Human Germ Project”:

In Ewald and Cochran’s view, evolutionary laws dictate that infection must be a factor in schizophrenia. “They announced they had the gene for schizophrenia, and then it turned out not to be true,” Cochran said one day when I mentioned genetic markers. “I think they found and unfound the gene for depression about six times. Nobody’s found a gene yet for any common mental illness. Maybe instead of the Human Genome Project we should have the Human Germ Project.”

I concur. Medical research should make much bigger investments in detecting, understanding the effects of, and developing treatments for human infections. Many existing lines of research, including many of the “autoimmune” and genetic hypotheses for disease origins, are not panning out, but continue to monopolize funding.

Jaminet’s Corollary

In the last century, sewage and water treatment has cleaned up our water supply and removed sewage and water as a vector for disease transmission. Hygienic methods, such as daily bathing and the use of soap, also tend to inhibit disease transmission.

Just as cholera is an extremely mild constituent of gut flora in hygienic Texas, but creates acute disease in unclean Guatemala, so we can expect that germs that created acute disease in (unclean) 1900 will have evolved to create mild chronic infections in (hygienic) 2011.

This is Jaminet’s corollary to the Ewald hypothesis:  Microbes are evolving away from severe acute disease toward milder chronic disease.

The focus of modern medicine on acute conditions, and its neglect of chronic conditions, adds to the selective pressures on microbes. Any pathogen that creates acute disease is subject to the full arsenal of modern antimicrobial drugs. But pathogens that create mild chronic disease are generally left untreated.

Modern medicine has created a powerful selective pressure on pathogens to generate chronic illnesses that are just mild enough, and that resemble aging closely enough, to elude the attention and antimicrobial arsenal of medical doctors.

Why No Dementia in Kitava?

Staffan Lindeberg in the Kitava Study found no evidence of stroke, diabetes, dementia, heart disease, obesity, hypertension, or acne on Kitava.

Why were these diseases absent? Partly due to the Kitavans’ excellent toxin-free diet, no doubt, but partly also due to an absence of the pathogens that cause these diseases.

Why was there no multiple sclerosis in the Faeroe Islands until British troops were stationed there in World War II? Because the pathogen that causes MS was absent from the islands, until the Brits introduced it.

Why has the incidence of chronic diseases increased tremendously in the last century? Partly due to longer-lived populations, but also, I believe, due to evolution of pathogens toward these diseases.

I predict the incidence of chronic disease will increase further in decades to come; and we will gradually come to appreciate that nearly all forty year olds today are not fully healthy, but are mildly impaired by a collection of chronic infections.

Conclusion

Fifty thousand years ago there were a few hundred thousand humans in the world. Today there are over 6 billion.

If a pathogen today wants to adapt to a specific host, its best bet is to adapt to humans. And within humans, its best way to flourish is to develop a chronic infection that persists for many decades.

The evolutionary arms race is not over. It has simply moved to a new field of battle. And medicine will have to evolve as the microbes do. The microbes are developing a new style of fighting. Medicine needs to shift its focus toward this rising threat of mild chronic diseases.