Introduction to Cell & Molecular Biology (BIOL121) - Dr. S.G. Saupe (ssaupe@csbsju.edu); Biology Department, College of St. Benedict/St. John's University, Collegeville, MN 56321

On Being Alive

"Life is nothing more, nothing less, than the structural organization of certain molecules".

Boyce Rensberger.  Science 80

I.What distinguishes animate (living) from inanimate (non-living) objects?
    This is not an easy question, largely because of the diversity of living things - no matter what definition you use, there will invariably be an exception.  Collectively, life is best described by its shared attributes.  These include:

A.  Life can be aesthetically understood and appreciated
   In other words, living things simply "look" alive.  Example:  rocks vs. fossils

B.  Life is diverse
    Although estimates of species diversity vary, we share the planet with at least 2 million, and as many as 30 million or more, other species.  This include organisms from bacteria (Monera) to amoebas (Protista) to fungi (Fungi) to squid (Animalia) to oak trees (Plantae).  Biologists currently recognize 3 major groups, or Domains, of organisms:  Bacteria, Archaea, and Eukarya.  The first two are prokaryotic (cells without a nucleus, no membrane bound structures within, genetic material in a circular loop), while the Eukarya, which includes plants, animals, fungi and protozoans, are eukaryotic (with a nucleus and membrane bound organelles).  

     The diversity of living things is the result of evolutionary processes, such as adaptation to the environment (see below), that have been occurring since life originated on the planet more than a billion years ago.   Among the evolutionary trends is increasing complexity of species that has been driven by accumulation and storage of genetic information.  Ancestral (primitive) species have given rise to others (called derived or advanced.   

C.  Life is variable
    Within a species, there is considerable variation from one individual to the next - simply look around to prove this.  This variation is largely the product of sexual reproduction and is the raw material for evolutionary change.  Without variations, species could not adapt and evolve.

D.  Life is organized
    Living organisms exhibit a high degree of organization of structure and function.  The human brain is described as perhaps the most complex structure known.  Matter in the universe can be arranged hierarchically (from greatest to least organization; or from largest to smallest; or from most to least complex; or from low entropy to high entropy):

Biosphere → ecosystem →  community → population → organism → organ system (in multicellular organisms) → tissue → cell →  organelle → molecule → atom

 Some Take-Home-Messages: 

1. Atoms are least complex, the biosphere most complex.
    

2. Each level must "obey" the laws of levels below it
    

3. Each level has unique properties that emerge from interactions at the lower levels.  These are called emergent properties, and they cannot be predicted based on knowing about lower levels.  Aristotle�s famous quote seems appropriate here, �the whole is greater than the sum of the parts.�
    

4. As a generalization, biologists, chemists, and physicists study different levels (from high to low)
    

5. Biologists can be classified by the level they study (cell biologist, histologist (tissues) or by the organisms they study (i.e., botanists = plants; mycologists = fungi)
    

6. Life is negatively entropic.  According to the Second Law of Thermodynamics � "all systems tend to a state of maximum entropy or disorder."  This occurs because "no energy conversion is 100% efficient", which is another way to state the 2^nd law.  You have probably seen the 2^nd law in action in your bedroom � it quickly enters a state of high entropy (disordered) unless you put energy into maintaining it neatly.  Similarly, to maintain an ordered, negatively-entropic state, living systems must constantly input energy (acquire and utilize energy).  Ultimately the energy is provided by the sun, incorporated into plants, and then passed to other organisms through the food chain.  
   
       As an aside, essayist and biochemist Harold Morowitz blames the discrimination of women on the 2^nd law � traditionally it was "women's work" to do housework, which is simply a battle against entropy.  As physicists know, you can never win the battle, only break even.  On the other hand, men's role has been to create and build new structures.  Check out his articles, "Six Million dollar man" and Women's Lib and the entropy crisis."
   

7. What is a biological individual?  Usually biologists consider an individual a separate unit that possesses its own unique genetic instructions.  Thus, it is obvious that you and I, squid, and oak trees are individuals.  However, there are some organisms that give us some problems.  For example there are some organisms that act as a single unit, but are made up of many individual units (i.e., slime molds, coral colonies, even bees).  If you accept our definition for individual what does that mean for identical twins?  Or, consider clones of creatures such as aspen trees.  These trees send out root suckers from a mother plant that are genetically identical.  These masses of plants can in some cases cover huge areas.  In fact, an aspen clone in Colorado has been found that covers more than 30 acres.  It is considered by many to be the largest (and perhaps oldest) organism ever to have lived on earth.
   
   

8. Cells (and levels above) are generally considered alive.  But:

• Can an organelle be alive?  To answer this question, let�s first ask a different question?  Where did you (or me or a squid or an oak tree) get your mitochondria from?  This is not such a silly question since these organelles, which are the sites of cell respiration (the cell powerhouse), cannot be made �from scratch� by the cell.  They arise only from other mitochondria which divide by a binary fission process.  Thus, we must have had them at birth.  They came from mom via the egg.  Where did mom get them?  From her mom (i.e., grandma) and ad infinitum?  So we can ask a good question - where did the first mitochondria come from? 
  
      There is good evidence that chloroplasts and mitochondria, and probably flagella, were once free-living bacteria.  About a billion years ago an endosymbiotic relationship developed in which bacteria, capable of either photosynthesis or respiration, took up residence inside another cell and evolved a dependence on the relationship.  These hitch-hikers then evolved into chloroplasts and mitochondria.  Thus, if true, from this perspective humans (and other eukaryotes) are simply large piles of bacteria aggregated into a complex transport and protective structure.  Evidence that supports this hypothesis is that mitochondria and chloroplasts, just like bacteria: (a) are the same size; (b) reproduce by the same mechanism (fission), (c) have the same type of DNA (a circle chromosome) and (d) make proteins in a similar manner.  Better call home tonight and thank your mom for your mitochondria.
  

• Can a molecule be alive?   How about a virus which is comprised of a core of genetic info (DNA or RNA) surrounded by a protein coat?  Although not generally considered alive themselves, they sure can do a lot of damage when inside a host cell.  What about a viroid which are RNA molecules that cause several plants diseases?  These are prions.  Holy mad cows, batman!  These are proteins that have been implicated in several diseases including scrapie of sheep and Jakob-Kreutzfeld. 
  

• Is the earth alive?  According to James Lovelock and Lynn Margulis, the earth is one gigantic self-regulating system, somewhat analogous to a giant cell.  By this view, life is almost more characteristic of the planet than individual species.  They call this idea the Gaia hypothesis. 

    Harold Morowitz (1983, "Two Views of Life") writes that, "Biological activity is then a planetary property, an interrelationship of organisms, atmospheres, oceans and continents�Environment and living organisms are bound, inseparable parts of one set of linked planetary processes�the sustained activity of the "biogeochemical" system is more characteristic of life than are the individual species".

9. Some observations about organization and the nature of life.
       Check out the quote by Boyce Rensberger, originally published in Science 80, that begins this set of notes.  This to me is a rather profound statement and as scientists we should ask what evidence supports this claim?  There is:

• Dehydration experiments (anhydrobiosis) with brine shrimp, yeast, tardigrades, and many others.  Consider the packet of active dried yeast that may be sitting in your refrigerator.  The cells in the package lack metabolism, reproduction, movement and all other criteria that make them "alive".  They are essentially in a state of suspended animation.  In their dehydrated state all they have is "structure".  When you add warm water, they "pop" back to life.  This phenomenon was first noted by the great microscopist Anton von Leuweenhoek. 
  

• Freezing experiments (cryobiology) with many different types of cells.  Again, in the frozen state the cells/organisms lack any life properties but warming will cause them to return to "life".  Cells can even be frozen to near absolute zero (cold by even Minnesota standards) � all that remains is structure.
  

• Could we ever create life in a test tube? 
      Why not?  Freezing and dehydration experiments show that it is theoretically possible...but technologically we are long way from mixing up something in the lab will crawl out of the test tube.  

E.  Life can move
    The Bible mentions the "quick and the dead".  Life shows movement at all levels of organization - atomic, molecular, organismal.  When my daughter Erin was young, she considered anything that could move, including sticks that she threw, to be alive.

F.  Life is self-regulating
    Or in other words, life is homeostatic.  Living things can maintain internal conditions within tolerable ranges.  (i.e., human body temperature, blood pH).  According to our text, "A major theme in the evolution of life is the development of increasingly complicated systems for maintaining homeostasis".

G.  Life is chemically unique
    99% of the elements in all living things (or things that were once alive) are carbon, hydrogen, nitrogen and oxygen.  In addition to these four are about 25 others that are required in very small amounts (micronutrients).  

    The elements in living organisms are linked primarily via covalent chemical bonds to form a diversity of different molecules.  These bonds are strong enough to hold the atoms together but not too strong that they can�t be broken as necessary.

    Organic compounds contain carbon, inorganic ones do not.  Thus, another feature is that �life is organic (carbon-based).�  The major organic molecules in an organism are:  (a) sugars  (carbohydrates or polysaccharides - like starch and cellulose) are built from simple sugars such as monosaccharides (like glucose); (b) proteins, which are built from amino acids; (c) lipids, which is a general term for any water insoluble molecule such as fat, waxes, oils and steroids; and (d) nucleic acids, like DNA and RNA, which are built from nucleotides.  Thus, �life is polymeric� - made of large molecules (macromolecules) that in turn, are constructed from smaller ones (monomers).

H.  Life is cellular
    The fundamental unit of life is the cell.  Cells are the "bricks" by which organisms are built.  This is one of the major paradigms of biology.  Named after monastic cubicles by Robert Hooke (1665).  The importance of cells was first stated by Schleiden and Schwann, in what is now called the �cell theory�:  all living things are comprised of one or more cells.  Later Virchow added all cells come from pre-existing cells (obvious now, but not to our ancestors who believed in spontaneous generation). 

I.  Life exhibits handedness
    Certain molecules can exist in two forms, a right- or left-handed form.  Solutions of these molecules will bend polarized light to the right or left, respectively.  Any particular organism will make only left or only right-handed molecules.  For example, sugars in organisms are primarily in the D (right handed) form, while amino acids occur in the L (left handed) form.  Louis Pasteur was the first to observe this phenomenon.  However, if these molecules are made non-biologically (like by a chemist), equally mixtures of right and left-handed are formed.

J.  Life is based on water
    Most organisms are made up of 70-95% water.  If the water content declines past a critical value, they either go dormant or die.

K.  Life can metabolize
    Carry out complex chemical reactions including photosynthesis, respiration and thousands of others (from protein production to hormone production to digestion).  When the Viking probe was sent to Mars it was designed to measure metabolic activity in the Martian soil.  It tested soil samples for evidence of gases that would indicate metabolic activity.  Although initial results suggested gas release, the activity seemed to be more akin to an Alka-Seltzer tablet dissolving in water.  One good metaphor is that life is like a flame - constantly burning energy, always changing, yet static in appearance.

L.  Life grows (increases in size, cell number) and develops (continuum of patterns that develop)
    Both must be carefully regulated.

M.  Life can reproduce
    Reproduction occurs at the cellular level (division by fission, mitosis or meiosis) and organismal level by sexual ("reproduction with variation") or asexual means (clones).

N.  Life has a plan
    Organisms contain genetic instructions, usually in the form of DNA.  All organisms use essentially the same genetic alphabet to specify their activities.  The genetic instructions are transmitted from parent to offspring.

O.  Life can adapt and evolve (or Life has a History)
    Adaptation is the ability, or result, of an organism to become more suited to its environment (i.e., owls have keen hearing and eyesight as adaptations to hunting and flying at night and cactus have needles and a fleshy stem as adaptations to dry conditions).  Adaptation results from evolutionary changes.  Evolution is the cumulative changes in species that occur over time; the process by which one species gives rise by descent from pre-existing species.  

    This is another major paradigm of biology.  Dobzhansky said, �Nothing in biology makes sense except in the light of evolution".  Why is evolution so important? � because:  (1) it explains the unity and diversity of life; and (2) it allows us to ask questions concerning the "purpose" of structures.  

    Darwin was the first to suggest a plausible mechanism by which evolution could occur.  His idea, natural selection, essentially states that individuals of a group that are best adapted to their environment will have more offspring than those individuals not as well suited.  Thus over time, the most adaptive features will appear with increasing frequency in future generations.

    Note that this idea implies that life is a continuum; life began once and has evolved into the diversity of organisms that have lived on our planet.  This explains the unity of life (we all share a common ancestor, some more recent than others) and the diversity of life (we have differing features because we are adapted to different environments/lifestyles).

    Imagine that living things are like the leaves on a tree with invisible branches/twigs.  The twigs, etc. are the lines of descent between individuals.  Those species that share a common twig are more closely related (share a more recent ancestor) than those species on separate limbs.  

Approximate sequence of evolutionary events:  

    lifeless Earth → chemical evolution (development of organic chemicals) → "life" (prokaryotic) → biological evolution (photosynthesis → eukaryotic organisms → multicellular organisms (as a result of cells changing shape, stick together))

P.  Life can fractionate isotopes
    Small amounts of radioactive isotopes exist in nature.  Plants absorb a higher percentage of non-radioactive isotope than would be expected.

Q.  Life interacts with the environment (ecology)

R.  Life responds to stimuli (or in other words, life shows irritability)     
    Punch someone and watch them respond.  Or, watch a plant bend toward a window.

S.  Life can die
    Here we are getting rather philosophical and circular in our reasoning, but I've included it to emphasize that death, from a biological perspective, is not bad.  It has many functions including helping to recycle resources and it serves as the vehicle by which evolutionary change is propagated.  An interesting way of looking at natural death is loosing the battle with entropy.  Levine & Miller (1994) say death "is equilibrium with the environment".


II.  Other features
      There are two major approaches to defining life:  (1) Chemical � entity with nucleic acids capable of replication and making proteins; and (2) Evolutionary � capable of reproducing and passing traits, but not identical traits, to offspring.

    There are other characteristics of life.  For example, Lewis Thomas argues in the "Music of the Spheres" that the urge to make music is a fundamental feature of living things.  

Some References (the italicized ones were consulted directly for this lecture):

• Bergeen, L.  Voyage to Mars:  NASA's Search for Life Beyond Earth.  Riverhead.

• Darling, David.  2001.  Life Everywhere:  The Maverick Science of Astrobiology.  Basic.

• Ferris, T.  2001.  Life Beyond Earth.  Simon & Schuster.

• Goodsell, DS.  1993.  The Machinery of Life.  

• Kauffman, S.  2000.  Investigations.  OUP.

• Koerner, D & S LeVay.  Here Be Dragons: The Scientific Quest for Extraterrestrial Life.  OUP.  

• Murphy, Michael.  1995.  What is Life?  The Next Fifty Years.  Cambridge University Press.

• Rensberger, Boyce.  1980.  Life in limbo.  Science80.  pp 36 � 43.  November.

• Sole, R & B Goodwin.  1999.  Signs of Life:  How Complexity Pervades Biology.  Basic.

• Stick, JE.  2000.  Sparks of Life:  Darwinism and the Victorian Debates Over Spontaneous Generation.  Harvard University Press.

• Ward, PD & D Brownlee.  2000.  Rare Earth:  Why Complex life is so uncommon in the universe.  Copernicus.

• Weisburd, Stefi.  1988.  Death defying dehydration.  Science News 133: 107 � 110. 

• Wolfe, Davide.  2001.  Tales from the Underground:  A Natural History of Subterranean Life.  Perseus.

• Young, Stephen.  1985. The dry life.  New Scientist.  31 October.