Setion I: Introduction to Cell Biology 

The Origins of Cells 

        Where did the first cells come from?

        How does one study the origins of cells, when we weren't there to see it happen?

        How could small organic molecules evolve the complexity of today's living cells?

        Can we identify exactly what it takes to make a cell?

   The age of the Universe is measured mathematically by how rapidly the universe is expanding.  The use of Hubble's constant, an estimate of the rate of expansion, suggests that the Universe formed some 12 billion years ago (bya). 

    Paleontologists study the forms of life in past geological periods by analyzing fossil remains through radiocarbon dating. Radiocarbon dating estimates age by measuring the decay of radioactive carbon, 14C, to nitrogen. Radiocarbon decays slowly to nitrogen in a living organism, and the amount of 14C lost is continually replenished, as long as the organism takes in air or food. Once the organism dies, however, it ceases to absorb 14C, so that the amount of the radiocarbon in its tissues will steadily decrease over time.  14C has a half-life of 5,730 years.  Half the amount of the 14C at any given time will undergo spontaneous disintegration during the succeeding 5,730 years. Because 14C decays at this constant rate, an estimate of the date at which an organism died can be made by measuring the amount of its residual radiocarbon present now. The oldest fossil rocks are estimated to have formed 3.9 billion years ago, with the oldest anaerobes near 3.5 bya, aerobes some 2.0 bya, and eucaryotes some 1.0 billion years ago. 

    Aerobic respiration, with the rapid accumulation of O2 as the Fe 2+ was used up in the oceans, is estimated to have become widespread about 2.5 billion years ago.  At present, our atmosphere is 21% oxygen. We are highly concerned about the recent shifts in the atmospheric concentrations of green house gases, as CO2 and methane.  Can you imagine what the bulletin headlines might have read-like 2.5 billion years ago.... "Government Sources Announce Catastrophic Consequences due to Increasing Oxygen Accumulation in Atmosphere........ Anaerobic way of life Threatened."  

    There appear to be four views on the origins of life and cells that are mentioned more than any other possibilities.  The first of these is the view of Supernatural Creation. The events here are beyond the descriptive powers of physics and chemistry. Each species of plant and animal is akin to a special reflection of a supernatural event, and homologies or anatomical similarities between species are assumed to be  associations of ideas in this special creation.  The canon of supernatural creation is based upon faith in which a supernatural being suspended the Laws of Chemistry and Physics to create life.  Supernatural Creation is not treatable by the tenets of the scientific method. 

    The second view has been put forth by a number of contemporary cosmologists, who are the astronomers of our time that deal with the origin, structure, and space-time relationships of the universe.  Some of these cosmologists suggest that life is a unique accident.  That its establishment was a singular event of unnatural possibility that is not likely ever to occur again.  The idea is akin to chance and may be similar to the shuffling of a deck of cards and dealing the four suites in numerical order.   (Rare Earth Hypothesis

    The third view is that life, or the molecular components of life, may have an original extra- terrestrial origin. The earliest proponent that life on Earth arose from a 'Panspermia' was the Swedish chemist, S.A. Arrhenius. He and many others, as Sir Francis Crick of DNA fame, proposed that microorganisms or spores wafted through space by radiation pressure from planet to planet or solar system to solar system. While a capable idea, it is extremely unlikely that any microorganism could survive over interstellar distances without being killed by the combined effects of cold, vacuum, and radiation. Even if meteorites are found on Earth with embedded microbes, who is to say that they didn't come from Earth, via Mars.  As we progress into the next Millennium, Panspermia remains a popular idea in our technological culture.  SETI, the Search for Extra-Terrestrial Intelligence via radio-telescopes heightens the human quest for its origins.   (extraterrestrial life forms)

    One tenet of a Panspermia origin is the real possibility that the base biolocules of life, simple organics as amino acids and nucleotides had an extraterrestrial origin in deep space and were then seeded on our planet by meteorite showers. Recently NASA scientists at the Ames Research Facility have conducted experiments combining simple organic chemicals inside a cold vacuum chamber that replicates the harsh conditions of deep spaceThey suggest that they have created primitive "cells" that mimic the membrane structures found in all living things.

By exposing chemicals -- that are known to exist in the swirling interstellar clouds of space which are the birthplace of stars and planets -- water, methanol, ammonia and carbon monoxide -- to ultraviolet radiation, the NASA scientists created primitive proto-cells similar to those found in everything from the cells of microorganisms to human beings.

Even though they were formed at temperatures close to absolute zero -- minus 441 degrees Fahrenheit -- when these artificial cells were immersed in water, they spontaneously formed simple membrane structures that contained both an inside and an outside layer. (see journal article - PNAS)

Mankind's ideas of ALF's or ET 


    The fourth and most plausible scientific view on the origins of life is referred to as Chemical Evolution. The main principles upon which Chemical Evolution is built is that all of the molecules, which we can easily find in known living cells, are made from the same small number of chemically reactive functional groups (-OH, CO 2, -NH 2, -COOH, -PO 4, -SH).  These reactive functional groups helped form the known polymeric macromolecules so common to the living condition.  It is these macromolecules which have been selected for by evolution over time, for they favor the energy transformation and self-replicating properties of living cells.  

    A major tenet of Chemical Evolution is the phenomena of Self-Organization, the view that the Natural Laws of Chemistry and Physics channel matter toward states of greater complexity.  Matter evolves naturally and automatically along paths of evolution leading to greater organizational complexity.  At some point this complexity of molecular interactions may have crossed a threshold and exhibited the properties we now know as the living condition.


"It was a dark and Stormy night"

    In 1922 Alexander Oparin and John S. Haldane hypothesized that the early Earth had a reducing atmosphere, rich in ammonia, methane and water.  With the presence of energy in the form of heat, UV radiation, pressure, and/or lightning the formation of small organic molecules from these simple inorganics would have been favored. In 1953 Stanley Miller and Harold Urey at the University of Chicago demonstrated in their lab the formation of small organic molecules, such as formaldehyde and amino acids, from such a primordial soup. (see figure of Miller & Urey apparatus) 

    One can envision five steps in the sequence of events in the progression of chemical evolution from molecule to living cell.  

First would be the abiotic synthesis of small organic molecules as earlier demonstrated by Miller and Urey (see above). Chemical catalysts as Cu, Zn, and Fe would have easily helped form hydrogen cyanide and formaldehyde, which could lead to the formations of sugars, amino acids, and nucleotides.

The second step would have to have been the autocatalytic assembly of polymers from these abiotic monomers, not unlike what we can see in today's cells. Formations of polymers made of peptide bonds and molecules with peptide and/or phosphodiester bonds would have a chemical advantage and have been highly selected for. 

    The establishment of a hereditary information blueprint would be the third needed step.  Three events in the formation of a hereditary apparatus would seem to be required: a) complementary templating, b) formation of unique sequences and polymeric catalysts, and c) errors in the replicating  process.  Based upon what we know today about complementary templating and the action of DNA and RNA, we might have expected some unique sequences of primordial polynucleotides to have formed the ability to catalyze a reaction that leads to the production of more molecules of the catalyst itself, i.e., self-replication (ribozymes). Such a property would have been highly favored and selected for from among the primordial soup of molecules being made abiotically.  Some of these unique sequences of polymers might have had specific 3-dimensional folds and unique shapes, not unlike the catalytically active RNA ribozymes of today, which would favor their eventual survival.  Errors in the complementary sequencing would allow new variants to form.  Thus these early catalytic complementary templating molecules would have a genotype, i.e., information in a unique sequence, which could be passed along by copying itself.  A phenotype for these molecules might be seen in their unique 3-D conformations, which allowed them to interact with other reactive molecules.

    The fourth step would almost certainly have to be the linking of self-replicating RNA molecules to the formation of simple polypeptides.  While no one has been able to demonstrate such an ancient link, we do know that today's cells use RNA complementary templates (messenger RNA's) to guide the synthesis of proteins in all living cells.  The missing link, so to speak, might be a catalytically active RNA (transfer RNA) which binds amino acids and leads to eventual polymer formation, just as in today's cells.  We know that the genetic code, which is expressed in RNA, specifies known amino acid sequences, and that the genetic code is universal to all living cells.  Thus the establishment of a chemical means to link these two processes would have been highly advantageous and selected for and may even be circumstantial evidence that a single ancestral cell, with such properties, may have given rise to all of today's cells.   

    The fifth step would be the encapsulation of these chemical's replicative processes.  The formation of membranes would have been a crucial event in the formation of the first cells.  Protein coding pieces of RNA would have had no advantage and not be selected for until self-compartmentation was established.  Coacervates are aggregations of macromolecules with catalytic activity in droplets with fat-like boundary interfaces.  Coacervates possess different chemical properties than their surroundings.  A protobiont is a coacervate with specific encapsulated enzymatic properties. 

    The first cell may have been nothing more than a spontaneous assembly of phospholipid molecules into a micelle droplet-like structure enclosing a self-replicating mixture of RNA's, which could influence primordial enzymes protein synthesis.