Why We Get Sick

The New Science of

Darwinian Medicine
Fundacin Ciencia y Evolucin
Santiago de Chile
Randolph Nesse
The University of Michigan

The Gap
Ideographic

Medicine

Evolutionary
Biology

A Recent Flowering
On the Aims and
Methods of Ethology
Niko Tinbergen, 1983

Recent Meetings

Humboldt University
York Hull Medical School
University of Copenhagen
NESCENT meeting at Duke
American Institute for Biological Sciences
American Physiological Society
University of Arizona
Berlin Institute for Advanced Study
American College of Epidemiology
National Academy Sackler Symposium
Fundacin Ciencia y Evolucin, Santiago de Chile

Evolution in 2 Minutes

Selection happens
When members of a group vary
And those variations influence survival or
reproduction
the group WILL CHANGE OVER TIME.
Selection is not a theory,
it is a theorem!

Examples of selection

Your penny jar

What is on television
Products on the grocers shelf
Who is here today!

Natural Selection
When inherited
variations in a trait
influence the
number of
offspring, the trait
will change over
the generations.

Natural Selection
When inherited
variations in a trait
influence the
number of
offspring, the trait
will change over
the generations.

Dogs from Wolves in a Blink

Darwin: On the various contrivances by which British and foreign orchids

are fertilised by insects. London, John Murray, 1862.

Why would an orchid

have
A spur 30 cm. long?

Xanthopan morgani praedicta

Angraecum sesquipedale The Star Orchid of Madagascar

Deep time

1 mm of dust each year

Ideographic
How long does it take to fill the canyon?
Just one million years

What selection explains

Adaptation-Darwins BIG discovery
Why bodies work pretty well
Individuals whose bodies worked better
than average had more offspring, so over
time the average bodies work better and
better

The bodys perfection

The eye
The heart
The nephron
Regulation of clotting

An organ of perfection
1.
2.
3.
4.
5.
6.

Upper eyelid
Lower eyelid
Lateral angle
Medial angle
Lacrimal aruncle
Limbus

7. Iris
8. Pupil
9. Lacrimal papilla

10. Sclera
11. Plica semilunaris

A botched design
Blind spot
Vessels block light
Nearsightedness
Lens gets clouded
Lens gets stiff
Retinal detachment
Glaucoma

You could design a better body!

Eliminate wisdom teeth

Eliminate the appendix
Make bones stronger
Improve immune responses
Make blood clot more slowly
Make coronary arteries bigger
Install a zipper so babies can exit easily!

If it is easy to improve the body,

why didnt natural selection do
it long ago?

Two Kinds of Explanation Needed

No biological problem is solved until both the
proximate and the evolutionary causation has
been elucidated. Furthermore, the study of
evolutionary causes is as legitimate a part of
biology as is the study of the usually physicochemical proximate causes.
E. Mayr, 1982
The Growth of Biological Thought

Gertrude Stein on
Her Deathbed
The answer, the answer,
what is the answer?
The answer, the answer,
what is the answer?...
No, no thats not it.

What is the question?

Why has natural selection left the

body so vulnerable?
Parts of the body
are exquisite

Others are botched

Why?

The Old Answer: Natural selection is

just too weak to make the body better.

The New Answer

There are six reasons why natural
selection leaves the body vulnerable
to disease

Six Reasons Why Diseases Exist

Selection is slow
1. Mismatch: body in a novel environment
2. Competition with fast evolving organisms
Selection is constrained
3. Every trait is a trade-off
4. Constraints on natural selection
We misunderstand
5. Organisms shaped for R/S, not health
6. Defenses and suffering

Origins of Darwinian Medicine

"The purport of the following pages is an
endeavor to reduce the facts belonging
to animal life into classes, orders, genre
and species; and by comparing them
with each other to unravel the theory of
diseases".
Darwin, 1794
Erasmus Darwin
Opening paragraph of Zoonomia,

E Conchis Omnia (Everything From Shells! )

Erasmus Darwin 1731-1802

Origins of evolution in medicine

Erasmus DarwinPhysician
Robert DarwinPhysician
Charles DarwinMedical school dropout
Because he hated geology!

Darwinian (Evolutionary) Medicine

The enterprise of using the basic science
of evolutionary biology in the services of
medicine and public health

Darwinian MedicineNOT!

Not a method of practice

Not radical in any way
Not about improving the species
Not opposed to ordinary medicine
Not a source of quick cures
Not just about modern diseases
Not just about the value of defenses

Evolution: A basic science for medicine

Four lines of work in

evolutionary medicine
Nesse & Stearns, 2008
1. Infection and fast evolution
2. Constructing phylogenies

3. Evolutionary genetics
4. Why selection left our bodies vulnerable

1. MISMATCH

Atherosclerosis
Breast cancer
Allergy
Autoimmune diseases

Atheroma

Cholesterol levels

Modern American 200

20 pre-industrial
131
5 hunter-gatherer
123
Rural Chinese
127
Eaton, et al.

Quirks
Harmless genetic variations that cause
disease in modern environments

Myopia

Figure 1 (A) Percentage of patients achieving remission or response at week 12 or 24 after

initiating ova therapy. (B) Mean change in Crohn's disease activity index (CDAI, mean (SD)) for
respondents to ova therapy. CDAI <150 is remission. p<0.0001, week 12 or week 24 compared
with baseline (time 0).

Summers, R W et al. Gut 2005;54:87-90

2. Competition with other organisms

Avoiding the e-word

Antonovics, PLOS Biology, 2007

3. Every trait is a trade-off

Most genes are trade-offs

Gout

Uric Acid Concentration/SMR vs. MLSP

Uric Acid/SMR (mg/100ml)/(cal/g/day)

0.3

0.25

0.2

0.15

0.1

0.05

0
0

10

20

30

40

50

-0.05

Years

60

70

80

90

100

Why does the body make bilirubin?

More Bili Fewer Heart Attacks

Why Bilirubin?
Sedlak and Snyder,
Pediatrics, 2004

Why is there Aging?

Williams 1957

Selection cannot eliminate genes that

cause problems after wild individuals die
Selection will increase the frequency of
genes that give advantages in youth,
even if those genes eventually kill us all

If mortality stayed at
early adulthood rates throughout life

4. Constraints
Things selection just cannot do
Path dependence
Mutations

Path Dependence

Mutation
Mutations happen
Takes time to purge them
Random factors can make deleterious
mutations more common

5. Health is not selections goal

The vulnerable sex
Sex mortality ratio=
% Males who die in a year

--------divided by-------% Females who die in a year

M.R. > 1.0 means that proportionately

more males than females are dying

Australia
Belguim
Canada

Colombia
El Salvador
Finland
France
Greece
Ireland

Italy
Japan
Norway

Poland
Singapore
1

Russia
Spain
Sweden

Age Group

75+

70 to 74

65 to 69

60 to 64

55 to 59

50 to 54

45 to 49

40 to 44

35 to 39

30 to 34

25 to 29

20 to 24

15 to 19

10 to 14

5 to 9

0
0 to 4

M:F Mortality Ratio

Switzerland
Ukraine
USA

USA 20th Century

3.16602
3.1
3
2.9
2.8
2.7
2.6
2.5
2.4
2.3
2.2
2.1
2
1.9
1.8
1.7
1.6
1.5
1.4
1.3
1.2
1.1

6. Defenses and suffering

Defects
Seizures
Cancer
Paralysis
Jaundice
Injury

Defenses
Fever
Cough
Pain
Fatigue
Anxiety

Defenses
and Suffering
Why are defenses
aversive?
Why so much
unnecessary pain and
suffering?

Pain or suffering of any

kind is well adapted to
make a creature guard
itself against any great
or sudden evil.
Charles Darwin,
1887, pp. 51-52

If the immediate and direct purpose of

our life is not suffering, then our
existence is the most ill-adapted to its
purpose in the world.
Schopenhauer, 1851

Cold coming soon in Santiago!

How much shivering is best?

Just right?

Too little

Too much

Using drugs to block defenses

If natural selection is so great, why doesnt
blocking normal defenses cause great
harm?

The Smoke Detector Principle

False alarms are Normal
This is why we can block pain, cough
and nausea safely
(Except for that 1 time in 1000!)

Panic and Agoraphobia

Panic is a false alarm fight-flight response
The experience of panic seems to down-regulate
the panic threshold
Any hint of danger releases a panic response
When you have recently been the object of a
predator attack, agoraphobia is useful indeed!

Why isnt the Body better?

There are six good evolutionary reasons
1.
2.
3.
4.
5.
6.

Infection
Mismatch
Trade-offs
Constraints
Selection is for reproduction not health
Defenses and the smoke detector principle

Conclusion
Evolutionary
biology
is a crucial
basic science
for medicine