Injury and Toxins

Weve focused until now on pathogens, agents of infection

Weve looked at the many ways in which we have co-evolved with the organisms
that cause disease

But diseases are not the only sources of bodily harm

Injuries and toxins can also contribute to our downfall, even if we manage to
avoid infections

How have we evolved to avoid or escape such random encounters with fate?

How do we repair the damage if we cant avoid it?

We dont usually think of pain as a good thing

Pain is something to be avoided, no one wants to repeat a painful experience

And that is precisely what makes the sensation of pain so adaptive

Why and how do we experience pain?

Despite its central importance in our lives, we know relatively little about the
physiology of pain

Victims of chronic pain can only be treated by severing key nerves that conduct
the pain message through the spinal cord

Though we may not appreciate or understand the experience, we can easily

understand why pain is adaptive

Those without the ability to feel pain are usually dead before they reach 30

Dont know when they are being severely burned or injured, so dont pull away

Fear and anxiety are first cousins to pain

They are physiological mechanisms that help us to avoid injury

Body senses danger, makes us fearful, anxious

Prepares us for fight or flight

Pain tells us to stop what we are doing

Fear and anxiety keep us from making the same mistake again

Part of our evolutionary legacy is the mantle of fear evolved by our ancestors

Fear of snakes, spiders, heights, big predators, confined spaces

All healthy, adaptive as long as they dont lead to outright phobia

Many of these fears are innate, others must be learned (cultural transmission)

Genetic predisposition to avoid certain potential dangers

Nave lab-raised monkeys are not afraid of snakes

Show them video of a monkey reacting to a snake with fear, the nave monkey
becomes afraid of snakes

Not just copy cat behavior

Can show nave monkey a video of a monkey afraid of a flower

Doesnt make the nave monkey afraid of flowers

Modern world presents us with many new sources of danger and pain - autos, xrays, pesticides, firearms

We have no evolutionary basis for being afraid of these things

They are too new for natural selection to have operated on them

Regardless of the sources of pain, we can learn to avoid it, by observing or being
taught by others (parents etc.)

Our ability to reason, abstract, communicate allows us to learn to avoid invisible

sources of pain, like UV radiation, odorless toxic gas etc

Anxiety upsets us, but it can be our best friend

Dugatkin (1992) studied the adaptive benefits of fear

Dumped groups of defenseless little guppies into tanks with a ferocious predator,
small-mouthed bass

Observed the reaction of the guppies, broke guppies into three classes:

> Bold - showed little or no fear, no attempt to hide - no survivors!

> Ordinary - Swam away from the predator - 15% survived
> Timid - Actively hid from bass, 40% survived

Many kinds of injuries:

> Wounds - external cuts or tears of tissue.

> Bruises - internal rupture of blood vessels, often due to blunt impact

Many kinds of injuries:

> Structural failures due to exceeding the limits of mechanical properties of

structural tissues:

Broken bones or torn cartilage

Damaged ligaments (between bones) or tendons (between muscles and bones)
Torn fascia (cover and separate muscles), organ capsules, or mesenteries
Ruptured blood vessels

Many kinds of injuries:

> Degeneration - a variety of defects that result from the fact that we are adapted to
live only so long

> Autoimmune diseases - antibodies fail to distinguish self-antigens and foreign

antigens, results in an attack on ones own tissues

Many kinds of injuries:

> Damage from infection - growth, reproduction and dispersal of pathogens and
parasites, produces tissue damage, diverts resources from our biological functions

> Thermal damage - extremes of temperature will kill tissue

Bodys repair mechanisms are limited

Unlike many lower organisms

> We cant regenerate missing digits, limbs etc.

> We cant repair damage to the CNS

No evolutionary explanation for why weve lost the ability to regenerate tissues,
organs

Know proximate causes, but not the ultimate (evolutionary) cause

If we lose a finger, it does not grow back

Proximal cause - embryonic tissues and genetic signals that grew the finger in the
first pace are lacking in adults

Ultimate cause - unknown, may have to do with cost vs. benefit of repair

Loss of finger will hurt, may be inconvenient, but not disabling or life threatening

Nothing for natural selection to work with

Live with it

Remember that regeneration may have been selected against because it increased
the risk of cancer

Look at the regenerative abilities of different tissues, find a very suggestive

pattern

Those tissues that readily regenerate are also the tissues most likely to become cancerous

Remove the brakes on cell division, take a big chance that growth might become
cancerous

Not a problem for short-lived species like the red-spotted newt

Easily re-grow a limb, dont live long enough for cancer to be a real concern

OK for repair mechanisms with short-term benefits, regardless of long term costs

Injury can also result from toxic substances

We are naturally disposed to avoid toxic substances, or animals or plants that

contain toxins

Most of us have no problem picking up a frog

No natural aversion, frogs are cute (sort of)

Toads are another story

Most people would hesitate to pick up a toad

Adaptive aversion - the bumps on its back contain lots of toxic compounds

Many dangerous substances in our environment:

> Poisons - chemicals that cause injury, illness or death; inhaled, ingested, or
absorbed

> Toxins - poisonous proteinaceous substances produced by a plant, animal, or

microorganism with chemical properties that can injure us

> Venoms - toxins that are injected by animals through bite or sting to subdue prey
or discourage predators

Toxic substances are a frequent source of injury

Many of these dangerous substances are so new, we havent had time to evolve
defenses

Other toxins have been a problem throughout our evolutionary history

Most of these legacy compounds come from plants

Organisms create many complex organic compounds as by-products of their

metabolism

Many of these secondary compounds (= secondary metabolites) are toxic

Animal bodies have evolved excretory systems to remove these substances (ex.
urea) or to detoxify them (liver)

Plants, however, retain their secondary metabolites

Secondary compounds become a type of chemical warfare

Not harmful to the plant, but will injure any organism trying to eat the plant

Phenols, alkaloids etc. taste bad, give upset stomachs, even hallucinations!

Organisms that are well defended are often bright and colorful - warning
coloration

Bees, amanita mushrooms, monarch butterflies

Easy to demonstrate how quickly we learn to avoid those organisms after a bad
encounter

Monarch caterpillars feed solely on milkweed

Milkweed is laced with a potent toxin, a chemical analog of digitalis

All stages of the monarch are brightly colored (caterpillar, chrysalis, butterfly)

The Viceroy, which tastes fine (to birds, at any rate) has evolved to mimic the
Monarchs warning coloration

Birds used to eating Viceroys will actively seek out any butterfly with similar
colors

Classic experiments by L.P. and J.V.Z Brower (1958) on Blue Jays

Jays developed an appetite in the lab for the tasty Viceroy butterfly

After once eating a distasteful Monarch butterfly, quickly learned to avoid all
orange and black butterflies

Jays in adjacent cages learned the same thing solely by watching the experiment
performed on other birds!

The tobacco horn worm has a similar strategy

Larva of the hawk moth, eats highly poisonous Datura, a plant of the US
southwest

Stores the poison in its skin to defeat the plant defense and gain protection from
potential predators

Lizard, Cnemidophorus, defeats the horn worm's defense by biting off the head,
squeezing out the worm's insides and eating them without eating the skin

Many ways for herbivores to adapt to phytochemicals

> Vomit (expel toxins)

> Eat plant parts that are freshest, most rapid growth (no time to accumulate toxins)
> Eat least poisonous parts (dont taste as bad)

Many ways for herbivores to adapt to phytochemicals

> Keep poison from being absorbed by body tissues, excrete it

> Detoxify the poison - liver (ex. body turns cyanide to thiocyanate)
> Avoid it in future (sauce bernaise syndrome)

Fruit shows how complex plant/herbivore coevolution can be

Fruit evolved for seed dispersal

Offer a tasty, juicy reward to attract animals

Eat the fruit, disperse the seeds in excrement etc.

Dont want animals to digest the seeds themselves

Dont want animals to eat the fruit before it ripens (when seeds will be mature)

So ripe fruit is attractive, sweet, juicy

Unripe fruit is hard, bitter, unattractive, can even make you sick (little green
apples)

Seeds can taste bad, have toxic chemicals (like cyanide in apple seeds)

Whats a human to do?

Eat only ripe fruit

Breed strains with little or no toxin (potatoes come from the poisonous deadly
nightshade family - bred for food in the Andes, now low in toxins)

Vary diet, so only get small amounts of any given toxin

Cook or prepare food to destroy toxins or bind them

Acorns are bitter, inedible, high levels of tannin (up to 9%)

Yet acorns were the main food for Californias Poma Indians

Mixed red clay into the flour, clay binds a lot of the toxic tannin

A new and highly controversial theory claims that small amounts of toxins are not
harmful

In fact, they could actually be beneficial!

Edward Calabrese (U Mass) claims the principle of hormesis applies to toxins

Hormesis - substances can have a very different effect at different dosage levels

A glass of wine a day is OK, a gallon a day is not

At low dosage levels, toxins often have the opposite effect that they have at high levels

Toxicologists have always assumed that the effects of toxin are strictly dosage
related, declining at low dosage levels, but never disappearing

Calabrese says far from disappearing, at low levels the effects are actually
reversed

Has found many studies indicating this is true for a wide variety of toxic
substances and many different types of organisms

Tiny doses of dioxin, cadmium, or DDT, ex. actually help cure certain types of
cancers

Controversial to say the least!

Especially considering the way weve polluted our environment with trace
amounts of thousands of toxic chemicals

How ironic if this should turn out to be a good thing

Injury and toxins are a good example of how we can gain a fresh understanding of
age-old problems by considering them from an evolutionary perspective