For
many years, I have been teaching a subject in general biology classes that I
call the Ecology and Evolution of Disease. It includes the subject that is now
called Evolutionary Medicine (it now even has its own journal). I continue to
be amazed that no general biology textbooks seem to mention it.
I
grew up thinking what most people still think about health and contagious
disease. As Ogden Nash wrote, “A mighty creature is the germ, though smaller
than the pachyderm...” It was all very simple. Germs caused contagious
diseases. The solution was to kill the germs. Problem solved.
But
it is not so simple, and the book that opened my eyes to the real complexity of
health and disease was Man Adapting,
a 1965 book by René Dubos. It was an old book when I first read it in the late
1980s. It was ahead of its time, and maybe still is.
Dubos’s
main point was that health is a creative response. It is delimited by biology
and evolution but it is highly personal. That is, a disease can take a
different course in different individuals. Dubos said that, when we ask what
man is, we should not be satisfied with the answer that he was an ape. Instead, we should think of ourselves as ecosystems in which health is the result
of the proper balance of all of our physiological processes, as well as all the
microbial species that call our bodies home.
Dubos
wrote about how the human body is an integrated whole, and conditions of the
body can alter the course of disease. For example, stress can affect the immune
system, with the result that bacteria that are already present but unnoticed
can flare up into disease. This is now well known. The stress of viral disease
can make a person susceptible to bacterial infections such as sinusitis and
pneumonia, caused by “germs” that were already present. The stress of allergies
caused me recently to have severe sinusitis. We have all seen examples of
people who, from stress and its related habits such as smoking, seem to always
be sick. Also, Dubos may have been one of the first scientists to write
extensively about how an upset to biological rhythms can result in disease,
including infections.
And
the effects of stress can pass on from one generation to another. A mother
animal who experiences stress can have behaviorally abnormal offspring, and it
might result in part from the effects of stress on the prenatal environment of
the fetus.
Dubos
also included a lot of information about how Old World diseases killed up to 90
percent of many Native American and Polynesian populations, because they had
never evolved resistance to these germs. Why didn’t the Europeans die of New
World diseases? Because there weren’t very many. America was populated by
immigrants from Siberia, and Polynesia by people sailing long distances in
boats. Only healthy people could have made those journeys. This opened my eyes
to a whole new understanding of some parts of human history. After Dubos, many
historians have written about this.
An
important, and still often ignored, aspect of our body ecosystem is its
microbial inhabitants. Gnotobiotic animals (born, raised, and maintained in
totally sterile conditions) are abnormal. Their organs develop abnormally, and
so do their immune systems. They heal more slowly from injuries.
Many
parts of our bodies, especially the skin and digestive tract, harbor trillions
of bacteria, most of which are harmless, and some of which are beneficial. Some
of the beneficial ones produce molecules which, to them, are wastes, but to us
are vitamins, especially B vitamins. In our intestines, the lactobacilli and
bacteroides are beneficial, while bacteria such as the famous E. coli are usually harmless. E. coli just seem to be along for the
ride. In rodent colonies with normal intestinal bacteria, kept in total
isolation from the outside environment and other rodents, the E. coli gradually disappear, leaving the
lactobacilli and bacteroides to dominate. But even the merely non-harmful
bacteria can do us some favors by crowding out the pathogenic bacteria.
This
is the ecology of disease within a human body. (There is also the ecology whereby
bacteria spread from one host to another.) But evolution also plays a role.
This was the book where I first read about how many disease organisms have evolved to become less virulent. For example, many diseases, such as smallpox,
leprosy, and (a disease Dubos and his wife studied) tuberculosis became less
and less deadly over the course of many decades even before the introduction of antibiotics and antiviral therapy. Some
infectious diseases have pretty much evolved themselves out of existence. One example
is the English sweating sickness, which was a severe plague from 1485 to 1551. Its
main symptom was profuse sweating. Then it vanished. Perhaps, Dubos speculated,
it evolved into such a mild form that nobody noticed it after 1551.
I
knew he was right as soon as I read his book, because I could think of my own
stories. I had read many gruesome stories about smallpox. But my own
grandmother had smallpox. For her, it was a severe but not deadly disease, and
did not leave pock marks when she recovered. She had become infected with a
relatively mild strain of smallpox. Before the WHO began its campaign of
worldwide vaccination to eradicate it, smallpox was already on its way out. I
also knew this from direct experience. I grew up in Tulare County, California,
after which the disease tularemia is named. It is endemic to the area, and
probably everyone who lived there had gotten it. Only, for us in the twentieth
century, it was a mild disease that we mistook for the flu. I did not know I
had had it until I tested positive for tularemia antibodies when I was a
teenager.
How
can a disease evolve to become milder? The simplest explanation is that a
horrible germ that quickly kills its host cannot easily spread to a new host
after it kills the first host. The first host is too sick to get up and spread
germs around, and everybody stays away from him if he tries. Also, some people
are naturally immune to the disease, and they are the ones who survive the most
often. But the main reason is that the mild
germs are the ones that are successful at spreading to new hosts.
This
is the evolutionary process of balanced pathogenicity. It was scientifically
demonstrated by a study on a rabbit virus, myxomatosis, in Australia in the
1960s. The rabbit populations evolved resistance to the virus, and the virus populations evolved into a
milder form.
I
got the impression from reading Man Adapting that balanced pathogenicity was
true of all infectious diseases. Of course, it is not. Cholera has not evolved
into milder form, because you get it from drinking contaminated water—water
that has been contaminated by very sick, or by mildly sick, people. You cannot
avoid the bad germs of the very sick people, mixed in as they are with the mild
germs of the mildly sick people. Also, malaria may evolve to become worse,
because mosquitoes like to bite sick people who cannot shoo them away, rather
than alert people who are busy. (However, Dubos pointed out, a person who is
very sick from malaria will die sooner, such that the mosquitoes might bite the
mildly sick people more often simply because there are more of them.)
It
was this book, Man Adapting, that
changed many of my views of science, making them less linear and more holistic.