Oldest fossils of a direct human ancestor are 5-6 MYA
Volcanos spew radioactive elements which become buried
Estimated that humans and chimps have evolved independently since 7 MYA
Hominin fossils fall into 3 primary groups, or genera:
Ardipithecus
Climbs in woodlands
Can walk on two legs
Australopithecus
Committed biped
Small brain
Big teeth and faces
Homo
Our genus – homo sapiens – are the only species remaining today
Technological primate; depends on culture
Found burial of dead (pets too) along with primitive instruments
Species
Age
Brain Size cm$^3$
Ardipithecus ramidus
~ 4.4 million years ago
350
Australopithecus afarensis
~3 to 4 million years ago
500
Australopithecus africanus
~2 to 3 million years ago
Australopithecus robustus
~1 to 2.5 million years ago
Homo habilis
~ 1.4 to 2.3 million years ago
650
Homo erectus
~ 200,000 to 1.9 million years ago
1200
Homo neanderthalensis
~ 30,000 to 300,000 years ago
1400
Homo sapiens
~ 200,000 years ago to now
1400
In addition to becoming larger specimen, brain size has increased rapidly 2 MYA of evolutionary history; resulting in ever more sophisticated behaviors. i.e…
Bipedality
Earliest trait
Change in hip/pelvis structure
Tool use
Nuanced social interaction
Language
Mathematical skill
Complex problem solving abilities
Capacity to construct elaborate explanatory frameworks to aid in understanding our world
Mammals and birds put in an incredible amount of energy into caring for their youn
This drives the nervous system to evolve for this
This behavior generalizes to complex social interactions
“Those communities which included the greatest number of the most sympathetic members, would flourish best, and rear the greatest number of offspring – Charles Darwin (1871)
Even though, biologically, caring traits are more beneficial than our fearful and violent impulses, our culture drives our choices
Our evolutionary experiment is still running… what qualities will be emphasized and selected for by our culture?
Written by Stanley Kubrick and Arthur Clarke in 1968
Clarke’s three laws give insight into the way we think about the world scientifically
When a distinguished but elderly scientist states that something is possible, they are almost certainly right. When they state that something is impossible, they are very probably wrong.
Generalizable
The only way of discovering the limits of the possible is to venture a little way past them into the impossible.
Any sufficiently advanced technology is indistinguishable from magic.
Context of aliens
How would we ever know, even if we say it? Consider natural phenomena we can’t explain
Movie shows hominin evolution starting 5 MYA
Hominins are human(-like) animals, including us and our ancestors
First scene shows the first act of intentional and willing act of killing on conspecifics
Human deaths due to violence in the 20th century: 150,000,000 - 200,000,000
Which transitions to…
HAL, the supercomputer, intentionally and willingly killing off the spaceship’s crew
HAL certainly appears to be operating as if it has intentions, reasoning, and even emotions
You need a subject, an ’experiencer’, to have consciousness; that is, awareness of our mental experiences
- Consciousness and mind are often used interchangeably
What is it like to be?
Freudian unconscious is Sigmund Freud’s (1856-1939) concept of how cognitive content out of our awareness may nonetheless have substantial impact on our behavior.
Because this content is mental, it has the potential to enter awareness
This is the goal of psychoanalysis: to bring unconscious things related to one’s behavior into consciousness, into awareness, where they can be subjected to analysis and become amenable to change
So to ask if HAL has a mind is to ask if HAL has an experience of what it is like to be HAL
Even if HAL can exhibit complex and intentional behaviors, we have no way of knowing if this accompanied by mental experience
What necessitates the mental experiences? Leads to thee….
Science literally means to seek knowledge, knowing.
Initially drawn to observing the stars: start of astronomy
Which lead to physics, rooted in math
Giving birth to chemistry
Started as tracking properties of matter
Evolved into our fundamental framework of atoms, molecules, electrons
and biology, the study of living organisms – which are the product of specific configurations of atoms and molecules
Which neuroscience emerges from!
Nowadays, we scientifically follow physical materialism (physicalism) – we conceive of the world ultimately being made of matter and atoms, made up of protons/neutrons/electrons, made up of quarks/neutrinos/mesons
These abstract particles are the fundamental ‘stuff’ of our universe
They energetically interact all the time and manifest these larger, more complex structures
Who are we? How are we related to everything else we believe we know and understand about the universe?
Modern science utilize’s an explanatory framework to investigate the physical and chemical interactions in living organisms
William James (1842-1910)
Pioneer in study of mind, wrote in his 1890 book The Principles of Psychology:
If the nervous communication be cut off between the brain and other parts, the experiences of those other parts are non-existent for the mind. The eye is blind, the ear deaf, the hand insensible and motionless. And conversely, if the brain be injured, consciousness is abolished or altered, even although every other organ in the body be ready to play its normal part.
That is, damage to the brain is associated with specific changes in mental functioning.
Therefore, wherever mental experience is coming from, the brain is clearly involved.
The nervous system: network that functions to manipulate external and internal information.
Specialized for rapid communication of signals throughout the body
Our brain is considered to be the locus of central control in the nervous system
Animals presumably have nervous systems to facilitate movement through the world.
Collection and analysis of sensory information and coordination with the mechanisms of movement are needed to safely accomplish the task of moving around in an environment that is often challenging and sometimes unpredictable.
Plants and fungi, the other kingdoms of multicellular organisms, do not move around in the fashion of animals and have evolved other, nonneural ways to flourish.
The human brain (together with the brains of a few other mammals) is perhaps the most complex structure known.
Composed of several hundreds of billions of cells interconnected by hundreds of trillions of connections.
Each connections is a locus of signal transfer between cells
Brains are made up of two general classes of cells: neurons and glia (Fig. 2.1).
It is currently estimated that there are around a hundred billion ($10^{11}$) nerve cells (neurons) in the brain and at least that number of glial cells (glia)
The cellular units of signal transmission are generally considered to be the neurons
Although many glia, especially the astrocyte glia, are also directly involved in signaling.
Figure 2.1. Nerve cell (left) and astrocyte glial cell (right).
… have been undergoing evolutionary refinement for hundreds of millions of years, and millions of years were required for the complexity of the human brain to develop among the primates.
Hundreds of millions of years of evolutionary variation and selection have led to these brains
The basic structure of all vertebrate animal brains is similar – can be represented as shown in Figure 2.4.
Develops in the embryo when a tubular structure (the neural tube) folds in and then closes off and expands at one end (on the left side in the diagram in Fig. 2.4).
The interior spaces of the tube will become the ventricles (fluid-filled internal spaces) in the mature brain.
Figure 2.4. Basic plan of the vertebrate brain
The three regions expand in the mature brain to contain millions of cells organized into distinct anatomical structures
The forebrain is dominated by the cerebrum
The midbrain is dominated by the optic tectum
The hindbrain is dominated by the medulla + cerebellum
Progressing from older fish, amphibians, and reptiles to (evolutionarily) more recent birds and mammals, the size of the cerebrum increases relative to the rest of the brain (see Figs. 2.5 and 2.6).
Figure 2.5. Brains of a fish (left) and a bird (right).
Many mammalian brains are distinct in that the structure of the cerebrum has bumps and groves (rather than being smooth)
The bumps and grooves are called gyri (singular: gyrus) and sulci (singular: sulcus)
Due to cerebrum being a folded structure
No folding: Mice, rats, and squirrels
Folding: Capybaras (the world’s largest rodents), dogs, cats, and primates
Figure 2.6. Brain of a mouse (a mammal); the cerebrum has covered over the midbrain (compare with Fig. 2.5).
Wrote book featuring some of the first, quality human anatomy drawings, published in 1543 in De Humani Corporis Fabrica – On the Fabric of the Human Body
Meninges: Three layers between skull and brain:
Dura mater: Skin-like sheet of tissue that covers the brain; from the Latin words meaning “hard or tough mother.”
Arachnoid: Delicate layer of tissue covering the brain below dura; from the Latin meaning “like a spider web.”
Pia mater: Third delicate layer; Latin for “soft or tender mother.”
Meningitis: Condition caused by inflammation (i.e through infection) of meninges; extremely serious occurrence because of its close proximity to the brain.
Figure 2.9. Open human skull with dura intact (left) and with dura peeled back (right); From Andreas Vesalius’s De Humani Corporis Fabrica (1543).
Sub-arachnoid space: …between the arachnoid and pia layers; contains…
Cerebrospinal fluid: liquid that cushions the brain inside the skull + transports soluble substances throughout the central nervous system
Vesalius, as well as other early anatomists, noted that the brain was highly interconnected via fiber pathways
Notable connections between
Brain with the sensory organs: the eyes, ears, nose, and tongue
Brain with the heart, and lungs, and digestive system
Spinal cord (which was contiguous with the brain) with muscles throughout the body
Seemed likely there was extensive communication between the brain and the rest of the body.
Figure 2.10. Autonomic and cranial nerve fibers connecting the brain and body (left), and nerve fibers connecting the spinal cord and the body (right), from Andreas Vesalius’s De Humani Corporis Fabrica (1543).
Early thinker on signaling in the nervous system; studied…
How the human body worked
How we are able to perceive the world
How the actions of the body are related to the subjective mental experiences of mind
Among his early writings, when he was in his thirties, were essays on the world (Le Monde) and on man (L’Homme)
Worried about publication in part because these essays addressed big questions about the nature of reality, perception, and mind.
At the same time (1630s)
Galileo Galilei (1564-1642) was being tried and sentenced by the Catholic Inquisition for heresy as a result of his writings on related topics of grand scope.
One theory was that this action was driven by fluid pressure of some kind, e.x. liquid or air. The fluid would be heated by the fire, resulting in increased pressure that forces it through channels up to the head and then back again.
Now we know that nervous system signalling involves the movement of charged particles
In Descartes’s time, electricity was just beginning to be understood.
1600s: Electricity was introduced into the English lexicon; Its origin being the Greek word for amber – elektron – the fossilized tree resin known for its properties of attraction: rub a piece of amber with a cloth, and the amber will attract light materials, such as hair or small pieces of paper.
1700s: Scientific luminaries were researching and writing about electrical phenomena.
Descartes was very interested in trying to understand perception – how is it we are able to sense the world, and how is it that physical sensations lead to mental experiences?
It seemed the eye captures light which signals somehow to the brain– but then what?
How can the physical sensations of light lead to our mental experience of the world—to visual perception?
Still an outstanding question now, four centuries later.
Figure 2.12. Dissection of muscles surrounding the eyeball
Figure 2.13. Visual perception and the action of pointing a finger
Found found legs severed from dead frogs could twitch when electrically stimulated
Hypothesized that muscles move as a result of internal electrical forces that can be triggered by external electrical stimulation (left)
Published in 1791: De viribus electricitatis in motu musculari, commentarius. – “Commentary on the effects of electricity on muscular motion.”
Galvani’s nephew,
Giovanni Aldini (1762-1834), continued his uncle’s work and contributed to increased public attention to connections between electricity and life.
Light could now be understood as a propagating wave of electromagnetic energy
Electricity was became increasingly central to all of physics.
As electricity became more a focus of experimental investigation, Galvani’s suggestion that neural signaling was electrical in nature continued to catch on.
1850: the German physician and physicist
Hermann von Helmhotz (1821-1894) measured the speed of an electrical signal moving along a frog’s nerve fiber, finding it to be about $100 \text{ kph}$
A few years later,
Walt Whitman (1819-1892) wrote a famous poetic line: “I sing the body electric.”
Nerve cells have a basic construction and biochemistry similar to all cells for all of life on Earth.
Examples:
Chromosomes containing genetic information, coded into the molecular structure of DNA.
Ribosomes where synthesis of proteins and their transport to desired locations within the cell.
Mitochondria which are dedicated to the generation of cellular energy.
All this is enclosed by a cell membrane: the structure that forms the boundary of the cell.
Within the cell there is also elaborate molecular scaffolding: composed of protein polymers called microfilaments and microtubules.
Far from being a bag of disorganized fluid protoplasm, a living cell is a highly ordered system of vast complexity.
Nerve cells (neurons) have dendrites and axons, specialized for the communication of signals from cell-to-cell
Nerve fibers (the thread-like structures connecting the brain with various parts of the body, Observed by Vesalius and Descartes in their dissections) consist mainly of bundles of axons.
Figure 2.15. Nerve cell, with axon and dendrites.
Microscopic analyses of the brain revealed it to consist of densely packed neurons and glial cells.
The elaborate interconnectivity of nerve cells in the brain was gorgeously illustrated in the drawings of two great pioneers of neuroscience,
Camillo Golgi (1843-1926) and
Santiago Ramon y Cajal (1852-1934), working in their respective countries of Italy and Spain at the beginning of the 20th century
Both were using a technique for staining neurons developed by Golgi in 1873, called…
Figure 2.16. Human cerebellar neurons drawn by Golgi (L) and neurons from human cerebral cortex drawn by Ramon (R)
While working as a physician in a large 500+ patient psychiatric asylum, Golgi, developed, in his “spare time”, his famous stain la reazione nera – the black reaction.
Made neurons, together with all their dendrites and axons, eminently visible under the microscope.
Here is the recipe, in brief, of his technique:
The dark crystals of silver chromate stain the neurons completely, rendering even very minute structures exquisitely visible. (In some variations of the procedure, glial cells are also stained.)
If every neuron in a small piece of brain tissue was stained in this way, the result would be a glob of dark-colored mess, so densely packed with silver chromate that it would be useless to look at in hopes of seeing individual cells.
Woefully inefficient: ~1% of neurons are stained!
These 1% are stained well while the others aren’t stained at all.
Still not known why only some neurons are stained!
Appear to be a random subset
May have to do with being recently (in)active– or something else about the recent state of the cell’s physiology
Brains and nervous systems were understood as sophisticated networks connecting sensory information with movement, having evolved in the animal kingdom to facilitate survival while moving around in complex and challenging environments.
Signaling in the nervous system was electrical in nature: it involved the movement of charged particles
These charged particles were likely to be atomic in nature.
The brain was recognized as somehow central to the functioning of the mind—mental experience and consciousness.
Developments in the sciences of physics and chemistry made it increasingly attractive to try to understand the phenomena of life at as microscopic a level as possible—that of cells and molecules.
There were many mysteries, many questions—but the future of the life sciences looked bright:
Nerve currents sparkle. A trillion nodes resonate. The mind engages.
To understand how nerve cells work – how they generate signals and pass information from one cell to another – it is essential to introduce a few basic concepts of chemistry
Matter: described in terms of its chemical elements, understood as atoms, which composed of protons, neutrons, and electrons
Chemistry: scientific field which investigates the conditions of how elemental constituents (atoms) interact to form larger entities called molecules.
Also concerned with the nature and transformation of matter
Involved with processes i.e. extraction, conversion, fermentation, distillation
E.x. metalworkers who ‘magically’ extracted metals from rock, and physicians who prepared extracts and essences from plants for healing the body and mind
Some alchemists sought the Philosopher’s Stone: a legendary substance rumored to transformation common metals (e.x iron, lead) into precious metals (e.x. gold and silver)
More importantly, there was a sect of alchemy concerned with investigation the psyche; a transformation of one’s self and the human psychological condition – a psychotherapy or vision quest
In this context, the Philosopher’s Stone is understood as a means for self-transformation; the method the alchemical practitioner achieves an integrated wholeness.
1869: Russian chemist
Dmitri Mendeleev (1834-1907) organized known chemical elements; created the periodic table
One of the great achievements of the human intellect, representing a large amount of information in a very compact form
Predicted the existence of several not-yet-discovered chemical elements through gaps in organizational scheme
- E.x 3 elements, discovered later, are now called gallium, germanium, and scandium
Chemical elements are represented by abbrvs:
H : hydrogen
He : helium
Li : lithium
C : carbon
N : nitrogen
O : oxygen
Na : sodium
Mg : magnesium
P : phosphorus
S : sulfur
Cl : chlorine
K : potassium
Ca : calcium
Fe : iron
U : uranium
Bk : berkelium
Identity of an element is determined by the number of protons (a type of positively charged subatomic particle) within its nucleus
Figure 3.1. Basic form of the modern periodic table of the chemical elements.
What are the chemical elements that make up living matter?
Carbon is the primary structural atom for building the large molecules making up living organisms,
But it’s not the most numerous – that’s water, which composes around 65% of humans
10 other elements also present & essential for healthy human life: magnesium, manganese, iron, cobalt, nickel, copper, zinc, selenium, molybdenum, and iodine
These are found in much smaller amounts
It is interesting to speculate as to what other forms of life might be possible Life without water, i.e silicone
Water is the canvas upon which life is painted, the landscape or stage upon which the molecular drama of life is played out.
Water is an example of a molecule: a stable configuration of atoms held together in a particular geometric shape by the sharing of electrons between atoms
Water = H$_{2}$O = H-O-H
Each hydrogen atom contributes one electron and the oxygen atom contributes two electrons for mutual sharing.
This sharing of electrons between atoms is called a covalent (chemical) bond
Shared electrons form a ‘glue’ that holds the atoms together.
Simple enough that electrons can be shown, but molecules are more commonly depicted as “ball” structures or “space filling” structures.
The molecules from which living organisms are built and the molecules that interact with living organisms are often more complex than the simple water molecule
Fluoxetine
Substance synthesized by chemists, marketed as a treatment for the mood disorder called depression.
Associated with the brand name Prozac
Drawn to the right in a diagrammatic way that has been developed in organic chemistry to represent molecules
Molecules produced by life (organic molecules, organic from organism) are composed largely of carbon and hydrogen and may contain dozens or hundreds or thousands of atoms
Largely from these four elements – carbon, hydrogen, oxygen, and nitrogen – are built the basic structures of an enormous number of biologically interesting molecules:
Hydrogen
Has one electron to share, so can form only one chemical bond at a time.
Has no possibility of forming the scaffold for a molecule
Can only be stuck around the edges
Carbon
Form the scaffold that defines the overall shape of the molecule
Has four electrons available for sharing, that is, each carbon atom can form four bonds and be covalently joined to up to four other atoms
This allows carbon to form the structural framework for molecules that can become very large
Oxygen
Oxygen has two electrons to share and so can form two bonds.
Nitrogen
Nitrogen has three electrons to share and thus is able to form three bonds
Primary psychoactive component of alcoholic beverages
Small organic molecule composed of 2 carbon atoms (C), 1 oxygen atom (O), and 6 hydrogen atoms (H) joined together by chemical bonds
Covalent chemical bonds, the sharing of electrons between atoms, are represented by lines connecting the atoms
Each carbon has four chemical bonds, reflecting four electrons to share; each hydrogen has one chemical bond, and the oxygen has two chemical bonds
The particular molecular shape produced by this geometric arrangement of atoms confers upon ethanol its peculiar properties.
Molecular structure diagrams show covalent bonds as lines. If there is no letter at the end of a line, assume a carbon atom is there. Any bonds not shown explicitly are assumed to be hydrogen, enough hydrogens so the total number of bonds per carbon equals four. Hydrogen atoms forming bonds with other elements are explicitly drawn in.
Here are some other relatively simple organic molecules – relatively simple in that they are built from linear chains of carbon and hydrogen, and nothing else
Organic molecules composed solely of carbon and hydrogen are called hydrocarbons.
The simplest combination of carbon and hydrogen consists of a single carbon atom bonded to four hydrogen atoms
This molecule is called methane
It is a gas that is combustible (burnable) in the presence of oxygen
In fact, it is so-called natural gas, obtained from fossil fuel deposits in the earth and shipped into our homes by pipeline to be burned in stoves and furnaces
The combination of two carbons and six hydrogens is called ethane; it is also a combustible gas
Three carbons and eight hydrogens make up propane, also a combustible gas that easily liquefies under pressure and thus can be more easily stored and transported in tanks
Four carbon atoms and ten hydrogen atoms form butane, an even more easily liquefied combustible gas
Five carbons make pentane and six carbons make hexane, both combustible liquids
Seven carbons make heptane and eight carbons make octane, also both combustible liquids
As the number of carbons grows larger, the liquids develop an oily consistency and get progressively thicker.
When the number of carbon atoms reaches twenty or more, the resulting substance is a waxy solid.
These molecules are fossils – molecular remnants originating with living organisms millions of years, or hundreds of millions of years, ago
Geological processes have transformed the once living material into hydrocarbons
Crude oil – petroleum (Latin petra = rock, oleum = oil) – is composed of a mixture of all these molecules and many more.
Petroleum refineries separate crude oil into its molecular components, making them available to be used as fuels and other materials in the modern industrial world
All these molecules are combustible – that is, in the presence of oxygen they can burn and release energy as the covalent bonds connecting the carbons and hydrogens are broken. Fossil fuel
Complete combustion will break all of the carbon-carbon and carbon – -hydrogen bonds and convert the hydrocarbon into a mixture of carbon dioxide (CO) and water.
Carbon, as well as some other atoms, also has the capacity to participate in bonds with other atoms in which it shares more than one electron
For example, in the ethylene molecule each carbon contributes two (rather than one) electrons to the carbon-carbon bond, forming what is called a double bond, drawn with a double line connecting the atoms.
Ethylene is also a combustible gas, often used in welding
However, the most widespread use of ethylene is to make polyethylene plastics by linking many ethylene molecules together in very long chains (polymers) of various shapes and forms.
The arrangement of carbons in a hydrocarbon molecule is not always linear
The chains of carbons may be branched, such as in this branched octane molecule.
The chain of carbons may even fold back upon itself to form a closed ring
Here is an example of that, the cyclohexane molecule.
Note that in all cases each carbon atom still forms four covalent chemical bonds and each hydrogen atom forms one covalent bond.
There is another cyclic arrangement of six carbons that occurs commonly in nature
It is now appreciated that, rather than an alteration of single and double bonds, all the carbon-carbon bonds in benzene are equivalent and are sort of intermediate between single and double bonds in strength
The shared electrons are best described as existing in molecular orbitals that encompass the entire ring structure
To represent this, the structural diagram for benzene is sometimes drawn witha circle inside the hexagon of carbons
While benzene itself does not occur in living organisms (it is a highly toxic and combustible liquid), the ring structure of benzene does occur widely as part of larger structures of many biological molecules
Let’s look at several of these that have relevance to the human nervous system.
Here are two famous molecules found in the brain, the neurotransmitters dopamine and serotonin.
While not the most abundant neurotransmitters in the human brain, these two molecules are perhaps the best known of the neurotransmitters, due to their frequent mention in the news media
If you were to randomly stop people on the street and ask them to name a neurotransmitter, if they had any idea at all as to what you were asking, they would likely answer with the name of one of these two molecules.
Notice that within the diagrams for these molecules the benzene ring structure occurs
Also notice that each of these molecules consists of a bunch of carbon atoms, several nitrogen and oxygen atoms, and a bunch of hydrogen atoms around the periphery of the molecule, all joined by chemical bonds so that a particular geometric shape results
Thus, these molecules are appreciated to be just a bunch of atoms (mostly carbon and hydrogen) connected together by the sharing of electrons (covalent chemical bonds) to form a particular geometric shape
It is their unique shapes that determine the properties of particular molecules within, say, the human nervous system.
If you spend time drawing a few molecular structures like those of dopamine and serotonin, you very quickly appreciate that mostly what you are doing is drawing lots of Cs (representing carbon atoms) and Hs (representing hydrogen atoms).
There may be a few other atoms, like the several oxygen and nitrogen atoms in dopamine and serotonin, but mostly there are Cs and Hs, lots and lots of Cs and Hs.
There can be so many Cs and Hs that it becomes difficult to notice the most important things about the molecule, such as the overall shape and what kinds of other atoms are part of the structure
Thus, chemists have developed a shorthand language for depicting the structures of organic molecules
In this shorthand language, the structures of dopamine and serotonin look like this:
Here we are simply not drawing the Cs and most of the Hs. We are drawing only the bonds connecting the various atoms together.
Although the six carbon atoms in a benzene-ring structure are diagrammed with alternating single and double bonds, the shared electrons are best described as existing in molecular orbitals that encompass the entire ring structure.
So now, at last, we can articulate the rules for drawing and interpreting molecular structure diagrams
Covalent bonds are drawn as lines
If there is no letter explicitly shown at the end of a line, then it is assumed there is a carbon atom in that location
Thus, each line (bond) has a carbon atom at either end, unless another atom is explicitly drawn
Atoms other than carbon are indicated: N for nitrogen, O for oxygen, P for phosphorus, F for fluorine, and so forth
What about the hydrogen atoms
Because we know that carbon forms four bonds, any bonds not shown explicitly are assumed to be with hydrogen, enough hydrogens so that the total number of bonds per carbon equals four
Hydrogen atoms forming bonds with other elements (such as nitrogen and oxygen) are explicitly drawn in.
One of the things we can easily do with this shorthand notation for molecular structure is compare similarities in shape between molecules
For example, one can see that these molecules – dopamine and norepinephrine, which are neurotransmitters; amphetamine, methamphetamine, and ephedrine, which are psychoactive drugs; and phenylalanine, an amino acid – all share a basic similarity of shape, something about their gestalt, or form.
In fact, they can all be chemically converted from one to another in straightforward ways, given the (R) conditions
And because of their similar molecular shapes, there are connections between what these molecules do in living organisms.
The three molecules below – tryptophan, an amino acid; serotonin, a neurotransmitter; and psilocin, a psychoactive molecule from Psilocybe mushrooms – all look somewhat similar to one another and different from the molecules pictured above.
Finally, here is another famous molecule – caffeine.
One sees that it, too, is simply a combination of rings of carbon and nitrogen atoms, together with a couple of oxygen atoms, but witha distinctly different shape compared with the other molecules drawn above
Again, these differences in shape determine the different functions these molecules have in living organisms.
Returning to water, a key reason that water is so important in living systems is that it is so very effective at dissolving things
Why is this so
The answer lies in a property of water known as polarity
In the water molecule (H$_2$O), the hydrogen atoms, being from the (L) side of the periodic table, are prone to giving up their electron and becoming positively charged
The oxygen, being from the (R) side of the periodic table, is prone to picking up electrons and becoming negatively charged
The result of these tendencies is that when the electrons forming the covalent bonds in water are distributed in the molecular orbitals describing the bonds, they essentially spend more time in the vicinity of the oxygen and less time in the vicinity of the hydrogens.
So the oxygen atom in water becomes slightly negatively charged and the hydrogen atoms in water become slightly positively charged
This is what is meant by polarity
Polar means separation, and in this case there is a separation of charge between different parts of the water molecule
Water is a polar molecule.
Water’s polarity causes the molecules to loosely stick to one another, a phenomenon called hydrogen bonding – the slightly negative oxygen atom of one water molecule is attracted to the slightly positive hydrogen atom of another (Opposite electric charges are attracted to one another.)
This results in a matrix of water molecules held together in a loose way by hydrogen bonds, depicted here as dashed lines.
Hydrogen bonding is noncovalent – it does not involve sharing of electrons
The water molecules are able to easily slip and slide past one another, producing the wateriness of liquid water
When water is heated the energy of the heat causes the molecules to jitter and shake more vigorously
At the boiling point, the jittering becomes vigorous enough to overcome the hydrogen bonding between water molecules, and the H$_2$O molecules escape as gaseous water – steam
Cool the water, and the molecular vibration lessens until, at the freezing point, the water molecules lock into a rigid matrix interconnected by hydrogen bonds – ice
The slight expansion of water when it freezes is due to the rigid matrix of hydrogen bonds taking slightly more space than when the molecules of water can slip and slide past one another in their liquid state.
The polarity of water also accounts for water’s amazing ability to dissolve many things, including ions
This can be illustrated by considering what is called table salt, sodium chloride (NaCl). A sodium atom (Na), being from the (L) side of the periodic table, very readily gives up an electron to form a positively charged sodium cation (Na).
A chlorine atom, being from the right side of the periodic table, will very readily take on an electron to form a negatively charged chloride anion (CI). Crystalline table salt, sodium chloride, can be described as an array of alternating sodium and chloride ions, held together by the electrical attraction of their respective positive and negative charges.
In the absence of water, NaCl is an extremely stable structure
However, introduce even a small amount of water and the NaCl will begin to dissolve, that is, fall apart into the water.
This illustrates water’s extraordinary ability to dissolve ions.
Because the charged ions are attracted to the opposite-charged portions of the polar water molecule, water molecules can slip into the otherwise very stable matrix of sodium and chloride forming the salt crystal
As the salt crystal dissolves, the cations and anions become surrounded with polar water molecules, attracted to the ionic charges
A saltwater solution is formed
Water is very effective at dissolving all kinds of atoms and molecules that have a net electrical charge (such as ions) or, indeed, any polar molecule, because the positive and negative separation of charge in a polar molecule will be attracted to the positive and negative separation of charge in the water molecule.
This allows us to introduce a very important concept into our description of solubility
Water, a polar molecule, dissolves (or loves to hang out with) other things that have polarity or charge
We call things that like to hang out with water hydrophilic (Greek hydro = water, philos = loving). Hydrophilic substances like to be around water, and water likes to be around them
At the other extreme of solubility in water, consider the hydrocarbons
These molecules consist only of carbons and hydrogens linked by covalent bonds
When electrons are shared among carbon and hydrogen atoms, the electrons are essentially equally likely to be found in proximity to either type of atom
Thus, there is no significant polarity, or separation of charge, in a hydrocarbon molecule and so nothing with which a water molecule can form a hydrogen bond
Thus, hydrocarbons don’t dissolve in water
This is illustrated by the well-known adage that oil and water don’t mix
Substances such as hydrocarbons that don’t dissolve in water – that don’t like to hang out with water – are called hydrophobic (Greek phobos = fearing). Hydrophilic things like to hang out with other hydrophilic things, and hydrophobic things like to hang out with other hydrophobic things.
Okay, so where is all this chemistry stuff taking us
Let’s return to the cell
Cells are the fundamental organizational units for all known living organisms
There are some characteristics shared by all cells, from bacterial cells to cells in the human brain
Among these shared features are a boundary membrane (composed of phospholipid bilayer), genetic material (composed of nucleic acids), ribosomal structures (for protein synthesis), protein receptors, pumps, and channels within the cell membrane, and so on
The component materials, the building blocks of a cell, are molecules, and the machinery of life, that which characterizes a cell as living rather than nonliving, is understood to be the chemical processes taking place within
Some of the molecules from which cells are constructed are quite large, consisting of thousands of atoms held together by covalent bonds
Below four fundamental types of biological molecules are described: lipids, proteins, carbohydrates, and nucleic acids.
Primarily hydrogen and carbon atoms in long chains; roles include energy storage, signaling within and between cells, precursors for neurotransmitters and hormones, and formation of membranes.
Phospholipids
Includes phosphatidylcholine
The phosphate group at the head is hydrophilic: will bind to water.
The hydrocarbon lipid tails are hydrophobic: won’t bind to water.
The fats or lipids (Greek lipos = fat) are medium-size molecules composed primarily of carbon and hydrogen atoms in long chains, generally sixteen to twenty-four carbon atoms long
Often there are a few oxygen atoms at one end of the chain of carbons
The roles of these molecules within cells are diverse and include energy storage (lots of energy is contained in the carbon-carbon and carbon-hydrogen bonds within the molecule), signaling within and between cells, precursor molecules the cell uses to make certain neurotransmitters and hormones, and formation of membranes enclosing cells and its interior structures.
A fatty acid is a kind of lipid molecule consisting of a hydrocarbon chain with a carboxylic acid group (-COOH) at one end
Palmitic acid is a sixteen-carbon fatty acid
It is called a saturated fatty acid because all the carbons are fully bonded with hydrogen atoms; there are no double bonds
Palmitic acid is very common in plants and animals.
It draws its name from palm trees and is a major component in palm oils.
Another example of a lipid molecule is oleic acid, an eighteencarbon fatty acid
Its name comes from oleum, Latin for “oil.” The chemical composition of olive oil is more than 50 percent oleic acid.
Oleic acid contains one double bond, and thus is an unsaturated (monounsaturated) fatty acid
The double bond is located nine carbons in from the end of the hydrocarbon chain, a so-called omega-9 fatty acid.
Because lipids are composed primarily of carbon and hydrogen atoms, they are largely hydrophobic in nature, preferring the company of other lipids rather than that of water
Lipophilic (lipid loving) is synonymous with hydrophobic
And conversely, lipophobic (lipid fearing) means the same as hydrophilic
Oil and water don’t mix.
Of great importance in living organisms are the phospholipids.
These lipids are composed of two carbon-hydrogen chains (each chain generally sixteen to twenty-four carbons in length), joined together at one end by a group of atoms containing, in addition to the ubiquitous carbons and hydrogens, atoms of oxygen, phosphorus, and perhaps nitrogen
These latter atoms form bonds having polarity and sometimes even electric charge
Thus, phospholipids have a highly hydrophilic portion (the polar or electrically charged phosphorus-containing “head group”) and a highly hydrophobic portion (the two long nonpolar hydrocarbon chains, or “tail groups”).
Among the most abundant phospholipids in the cells of animals and plants are the phosphatidylcholines, an example of which is shown here:
The two hydrocarbon lipid tails, here both eighteen carbons long, may be of varying lengths
The head group contains a phosphorus atom, multiple oxygen atoms, and a nitrogen atom that carries a positive charge
The positive charge comes from an electron deficit arising from the nitrogen having four bonds with other atoms, rather than its customary three
This configuration is called a quaternary amine.
The peculiar structure of phospholipids, with their distinct hydrophilic and hydrophobic portions, gives rise to a remarkable phenomenon when these lipids are present in an aqueous (water) environment
When surrounded by water, phospholipids will cluster together such that the hydrophobic/lipophilic tail groups associate with one another and the hydrophilic/lipophobic head groups associate with one another
Moreover, the hydrophilic head groups want to be in contact with the water environment and the hydrophobic tail groups want to be protected from contact with the water environment
To accomplish this, they form a double layer of phospholipid molecules (Fig 3.2): the hydrophilic head groups form the exterior surfaces (in contact with one another and in contact with the water environment), and the hydrophobic tail groups are inside the layers (in contact with one another and shielded from contact with the water environment by the hydrophilic heads).
Figure 3.2. Diagram of phospholipid bilayer: the head groups, represented as small circles, are to the outside of the bilayer, and the hydrocarbon tails are inside. There would be water above and below the bilayer.
Phospholipid bilayers form sheets in three dimensions that can fold to form enclosed surfaces separating two aqueous environments, such as the inside and outside of a cell
Indeed, phospholipid bilayers constitute the membranes forming the boundary layers around all cells for all of life on Earth
The cell membranes of bacteria, of plants, of mushrooms, and of brain neurons all have the same fundamental structure: a bilayer of phospholipid molecules
It is one of the most beautiful and elegant structures in the known universe!
These phospholipid bilayer membranes are very tiny structures, with thicknesses of only about 5 nanometers (5 x 10-9 meters, or five billionths of a meter).
The phospholipid bilayer membranes of cells contain a diversity of protein molecules that serve a variety of functions vital to cells
In nerve cells, among the various membrane proteins are ion channels, ion pumps, neurotransmitter receptors, and neurotransmitter reuptake transporters
In an actual biological membrane, the density of membrane proteins can be quite high, and the proteins will have a variety of wild and crazy shapes (Fig
3.3).
The molecules that make up a phospholipid bilayer are constantly jiggling as a result of thermal vibration, and there can be quite a lot of mobility of the proteins and other molecules within a biological mem- brane
In many ways, these membranes are more like fluids in their properties than they are like solids.
Proteins are made of amino acids, which are molecule that contain both an amine group (-NH$_2$) and a carboxylic acid group (-COOH).
Proteins are large molecules built from amino acids linked into long chains by covalent chemical bonds, called peptide bonds
So, first, what is an amino acid?
In organic chemistry, an amino acid is a molecule that contains both an amine group (-NH2) and a carboxylic acid group (-COOH).
The amino acids used as protein building blocks by all life on Earth are characterized by having amine and acid groups linked to the same carbon atom; these are termed alpha-amino acids
Here R represents a portion of the molecule containing other atoms
Different amino acids are characterized by having different R groups
The simplest amino acid has R = H
This amino acid is called glycine
The next simplest has R = -CH3. This is alanine
Another amino acid, called phenylalanine, has an R group consisting of a carbon attached toa benzene ring
Life on Earth uses twenty different amino acids (characterized by twenty different R groups) as the molecular building blocks of proteins.
Figure 3.3. Phospholipid bilayer forming a biological membrane
Membrane proteins are here depicted as amorphous, potato-like structures
In actuality, proteins have a great deal of internal structure.
Here is a representation of two amino acid molecules, with all the atoms drawn out explicitly:
The R groups, R$_1$ and R$_2$, may be the same or different
If amino acid molecules are simply mixed together in water and shaken up, nothing happens – they do not spontaneously join together to form chains.
However, in the appropriate environment inside living cells, amino acids can join together with peptide bonds to form a chain of amino acids called a polypeptide.
Here is the molecular structure diagram of how two amino acids can join together into a dipeptide by the formation of a covalent bond between them
This joining does not happen spontaneously but only under specific catalytic conditions found within the ribosomes of cells
Ribosomes are structures inside cells that are built from proteins and nucleic acids
They are the sites of protein synthesis within cells, with enzymatic activity of the ribosome facilitating, or catalyzing, the formation of covalent bonds between amino acids
The diagram above shows that an -H and an -OH are removed in the formation of a peptide bond
They will produce one molecule of water, HzO, which floats away
You can also see that the two ends of the resulting polypeptide structure have an amine group and an acid group available to form additional peptide bonds
Thus, it is possible to form very long chains of amino acids, covalently linked by peptide bonds
Ribosomes provide the conditions for this to take place.
When a bunch of amino acids link together to form a polypeptide chain, they fold around and form a shape
Similar to water flowing downhill, the polypeptide chain folds in such a way so as to arrive at a lowest-energy configuration, determined by the myriad attractions and repulsions among the component atoms
Thus, the chain of amino acids develops a unique three-dimensional shape, and it is this shape that will help determine how it functions in the cell
Any chain of amino acids is called a polypeptide; if it is more than about forty amino acids long, then it is called a protein
The threshold number for defining when a polypeptide becomes a protein is somewhat arbitrary
Some might say thirty, some fifty.
Figure 3.4 is a diagram of a small protein called myoglobin
It is a chain of 153 amino acids that binds, stores, and transports oxygen molecules within animal muscles
In this drawing, myoglobin is depicted as a ribbonlike structure representing the polypeptide chain and overall shape of its folding
The chain of amino acids spontaneously folds into a stable configuration characterized by an energy minimum
The result is a unique three-dimensional structure for the protein
In addition to its 153 covalently linked amino acids, myoglobin contains a component called heme (not shown in this diagram), a planar molecule embedded within the protein’s structure that functions to bind a molecule of oxygen
The diameter of myoglobin is only about two nanometers; even though proteins are considered relatively large molecules, they are still very tiny indeed.
Figure 3.4. Myoglobin molecule.
In describing proteins, several descriptive levels of structure have been defined
What is called the primary structure of the protein is the linear sequence of amino acids forming the protein – a list of the component amino acids in the order they occur in the polypeptide chain.
The secondary structure describes the interactions of nearby amino acids to produce patterns of local folding within the protein
Nearby amino acids may interact with one another via hydrogen bonding and other sorts of electrical attraction and repulsion
This may give rise to distinct varieties of local folding within the protein
The most famous example of protein secondary structure is the alpha helix, first described by the great chemist
Linus Pauling (1901-1994). In Figure 3.4, alpha helices are represented by twisted sections of ribbon.
The tertiary structure is the overall shape of the entire protein molecule, created by all the electrical and geometric properties of the constituent amino acids guiding the folding of the chain of amino acids into a unique three-dimensional form.
Many functional proteins in living organisms are composed of a complex of more than one polypeptide subunit, with each subunit generally consisting of hundreds of amino acids
Such an arrangement is termed the quaternary structure of the protein
For example, hemoglobin – which binds and transports oxygen in our blood – is composed of four polypeptide subunits
And ionotropic receptors for the neurotransmitter GABA (see Chapter 6) are composed of five subunit polypeptides.
Built from atoms of carbon, hydrogen, and oxygen, which store substantial amounts of energy in their bonds.
Small molecules include sugars such as glucose
Large molecules include glycogen, cellulose, and starches. Starches consist of polymers of hundreds or thousands of glucose molecules linked by covalent bonds.
Our third category of biological molecule is that of carbohydrates
The name comes from a conjunction of carbon (carbo) and water (hydrate), and carbohydrates are built from atoms of carbon, hydrogen, and oxygen, covalently joined to form molecules
Some carbohydrates are small molecules, such as the sugars glucose, fructose, and ribose.
And some carbohydrates are enormous molecules, such as glycogen, starches, and cellulose
Starches consist of polymers of hundreds or thousands of glucose molecules linked by covalent bonds into very long chains
As with the fats, substantial amounts of energy are stored in chemical bonds joining the carbon, hydrogen, and oxygen atoms, and carbohydrates serve as sources of fuel for living organisms.
The fourth and final category of biological molecule to be introduced here is that of the nucleic acids, represented by DNA (deoxyribonucleic acid) and RNA (ribonucleic acid).
DNA and RNA are by far the largest molecules in living organisms, containing many thousands, even millions, of atoms and serving as the repositories for the information required for constructing a living cell – the genetic or hereditary information
The DNA double helix is composed of two very long chains of four component nucleotides – adenine (A), cytosine (C), guanine (G), and thymine (T) – coupled with deoxyribose sugars and phosphate (phosphorus and oxygen) groups
Each long chain is held together by covalent bonds between the sugars and phosphates
The two chains wind around one another in a helical form and are held together by noncovalent hydrogen bonds between nucleotides
Adenine forms hydrogen bonds with thymine, and guanine forms hydrogen bonds with cytosine.
The discovery of the double-helical structure of DNA and its ramifications is one of the great sagas of twentieth-century science
The field of molecular biology and the modern biotechnology industry were among the offspring of this discovery
Also, among the ramifications, I believe, was the strengthening of confidence that the known chemistry of atoms and molecules will be able to account for all the phenomena of life, including even that of mind and consciousness.
So, let the tale betold… Molecules and cells, atoms play their varied roles. Theater of life!
Figure 2.1. Nerve cell (left) and astrocyte glial cell (right).Figure 2.2. Compass jellyfish, Chrysaora hysoscella, from 1904 book Kunstformen der Natur (Artforms of Nature) by Ernst Haeckel.
Figure 2.3. Planarian nervous system.
Figure 2.4. Basic plan of the vertebrate brain
Figure 2.6. Brain of a mouse (a mammal); the cerebrum has covered over the midbrain (compare with Fig. 2.5).
Figure 2.9. Open human skull with dura intact (left) and with dura peeled back (right);
Figure 2.10. Autonomic and cranial nerve fibers connecting the brain and body (left), and nerve fibers connecting the spinal cord and the body (right), from Andreas Vesalius’s De Humani Corporis Fabrica (1543).
Figure 2.12. Dissection of muscles surrounding the eyeball
Figure 2.13. Visual perception and the action of pointing a finger
Figure 2.16. Human cerebellar neurons drawn by Golgi (L) and neurons from human cerebral cortex drawn by Ramon (R)
Figure 3.4. Myoglobin molecule.
