Transcript Darwinian Medicine

How do we compete with pathogens?
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Bacteria and viruses reproduce much more rapidly
Bacteria and viruses are very numerous
Bacteria and viruses tolerate vast fluctuations in population size
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Recover so quickly
1% of bacterial population is insignificant but 1% of human population is a
major proportion
Enormous genetic diversity with rapid evolution
Summary: Pathogens have large populations that undergo rapid
fluctuation, evolving at a much higher rate than their hosts.
Pathogens have a shared interest in our
survival; with few exceptions, a dead
host inhibits the spread of the pathogen.
Evolutionary mechanisms include
intraclonal (within the cell) and interclonal
(between different cells) processes.
Intraclonal Processes
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DNA Replication: microbes are constantly exposed to chemical and
physical mutagens, resulting in high variation of genomes
RNA Replication: no repair mechanisms means a mutation rate so
high that for many RNA viruses virtually every particle is
genetically different
Haploid Organisms: single copy genomes means no delay in
expressing new genetic factors
Phase Variation: many pathogens seem to have an archive of
genetic material that may be silent under normal conditions but can
become expressed and give the appearance of an adaptive change
Interclonal Processes
Genetic Exchange: conjugation, transduction, and
transformation increase the genetic, and often the
phenotypic, diversity
 Host-Parasite Coevolution: hosts and parasites coadapt
with parasites generally prolonging their survival by
overcoming host defenses and mitigating their virulence
 Symptoms: symptoms may be a host defense or a
virulence mechanism
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The Germ Theory of Disease
(Revisited)
Foundations of Microbiology
 Antoni
van Leeuwenhoek first observed
microorganisms
 Louis Pasteur laid the foundation for modern
microbiology
 Robert Koch developed methods and concepts
Koch’s Postulates
The disease-causing organism must be present in all
diseased hosts and absent in healthy hosts.
 The disease-causing organism must be isolated and grown
in pure culture.
 Inoculation of a healthy host with the disease-causing
organism must result in the original disease.
 The disease-causing organism must be re-isolated and
shown to be the same as was inoculated.
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Ignaz Semmelweis
 Observed
that mortality rate of new mothers was
higher with physicians than with midwives
 Suggested better hygiene to reduce mortality
 Friend died of puerperal sepsis contracted during
autopsy
 Hypothesized “invisible agents” responsible for the
spread of disease
The Germ Theory of Disease:
Microbes are responsible for
the spread of disease.
Leading Causes of Death in the U.S.
Darwinian Medicine:
The influence of evolution on disease.
 How
does a disease affect reproductive fitness?
 An inherited disease with a severe fitness cost will
be selected against.
“When diseases have been present in human populations
for many generations and still have a substantial negative
impact on people’s fitness they are likely to have an
infectious cause.”
---- Paul Ewald
Darwinian Medicine and
Microbiology
Evolutionary change occurs very rapidly in the microbial
world
 Evolutionary drive is to reproduce
 Do reproductive and transmission strategies influence
disease symptoms?
 Are disease symptoms caused by the pathogen or the host?
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Evolution of Infectious Disease
 Too
many copies of an infectious agent can kill or
immobilize a host before it can spread
 Pathogens transferred by a vector tend to be more
virulent
Chronic Diseases
Diseases that could not fulfill Koch’s
Postulates were attributed to heredity,
environmental, or “multifactorial” causes
Darwinian Medicine and
Microbiology II
Some of the diseases attributed to genetic or
environmental factors, including some forms
of heart disease, cancer, and mental illness,
are in many cases actually due to microbial
infections.
Heart Disease
 Clogged
coronary arteries have been found full of
Chlamydia pneumoniae
 Some estimates that 80% of coronary heart disease
is caused by C. pneumoniae
 C. pneumoniae also found in autopsied brains of
Alzheimer’s patients (not in controls)
HIV
 High
mutation rate
 Preventative measures curb the spread of infection
 Would transmission-prevention programs be more
effective than the search for a vaccine?
Cancer
 HTLV-1,
a retrovirus endemic in parts of Asia,
Africa, and the Caribbean, has been linked to some
leukemias and lymphomas
 Epstein-Barr Virus, the cause of mononucleosis,
has been linked to some lymphomas and
nasopharyngeal cancers
 HPV has been shown to cause cervical cancer
 Hepatitis B and C have been linked to liver cancer
Ulcers
 Barry
Marshall demonstrated that up to 75% of
ulcers may be due to Helicobacter pylori
 Over 90% of cases are cured with antibiotics
 Infection by H. pylori causes a 6-fold greater risk
of stomach cancer
Prediction from Ewald:
Throughout history most people have
died of infectious disease, and most
people continue to die of infectious
disease.