Early Historical Milestones in CMB... 
           Between 1860-1925  two new areas of biology evolve into CMB…
isolation & chemical characterization cell substances...     
    synthesis of 1st natural biological product in lab...
from urine &/or oxalic acid from spinach UREA                                                  
       1st macromolecule isolation free of cell... fibrous, acid precipitate  = protein         1838  Gerhardus Mulder
     isolation of nuclein from from nuclei of white blood cells & sperm of Salmon   1869  Friedrich Miescher

          1st cell free yeast extracts that convert glucose
  --> alcohol  (fermentation)         1897  Eduard Buchner

        structural makeup of molecules (peptide bond)...  16 of 22 amino acid discovered           1900's Emil Fischer
2. Genetics...
 study of inheritance/characters in plants & animals...     
       dominant/recessive; dihybrid crosses; value was quantitative approach                  
1865  G. Mendel
 [Mendel Web]
       chromosomal theory of inheritance  (Meiosis matches Mendel)
                                      1902  SUTTON & BOVERI
       "biochemical genetics" alkaptonuria- mutations = defective proteins
                         1902  Archibold GARROD
       coins term GENE + concepts phenotype & genotype                                                              1909  Wilhelm JOHANNSEN
       chromosome linkage & mapping (Drosophilia)                      
1911-1920's  T.H.Morgan (paper) & Sturtevant
& Bridges
   what's important is concept of what was done (i.e., CELL FREE EXTRACTIONS), not specifically who did it.


3. Molecular Genetics...
isolation & chemical characterization cell substances...
            between 1925
to 1965 - Cell & Molecular Biology comes of age...
period of discovery of chemical nature of gene &  merging of biochemistry & genetics
              transforming principle (genetic agent causes pneumonia)                            1928  Fred Griffith  
       "one gene   =   one enzyme"                                                                                                 1941  G.Beadle  &   E. Tatum
proteases don't alter gene transformation, but DNAses inactivate
DNA is genetic material.
1st use of enzymes
             to test for
active biological activity
                                                                        1944  Avery, MacLeod & McCarty
         base complimentarity amounts of bases A = T and G = C                               1950  Erwin Chargaff
 experiments using 32P establish DNA as genetic material                            1952  Alfred Hershey bio & Martha Chase
         jumping genes (transposons)                                                                                           1944 - Barbara McClintock

Cell & Molecular Biology... integration of molecular structure & cell function...
            between 1950-1990 -   Birth of Modern CMB and Structural Biology... 
                  NHGRI Dynamic History Timeline  &   NHGRI Timeline Landmarks graphic      

 ...A Brief History of Biotechnology by Mallery

Foundations of Modern Cell & Molecular Biology, i.e,  Bil 255
n       1953 to 2007 is the dawn of the modern Molecular Cell Biology age
& is the content of Biology 255
      some personal relevance...
       my mother (nee 1906)
: saw advent of auto, airplane, radio, T.V., man on the moon...
          me (1943): heart transplants (who was 1st ?), rise of antibiotics, Rover & Phoenix on Mars,
                         DNA & transgenic animals,  artificial genes & manipulation, cloning, human genome...

CMB is part of our modern popular culture -
Movies: Jurassic Park &  Species-I   Movie-III
                      & is part of highest recognition in science is ?   Nobel Prize in Medicine & Chemistry

                          to reiterate...    The aim of Modern CMB is to interpret the
              properties of life & organisms through the
              structure of their constituent cellular molecules.


Some fundamental questions CMB asks ?

    How did life originate ?

    How does life beget life ?

    How does an individual (plant-animal) develop for a fertilized egg/seed?

    What is the progression from individual molecules
                                                         --> to multicellular organism?


  and some answers to these questions:
with the deciphering of DNA came our understanding of the Central Dogma...

               CMB gave us... the    Central Dogma of Molecular Biology 
                                           DNA --> RNA --> Protein        mcb fig 4.1*
            ¨   Early origin & evolution of cells must have
                    been the result of those cells which had developed self replicating molecules (RNA?)...
& thus had a better fit and likely were selected for evolutionary survival...


         " Life begets Life " - is now seen at the molecular level,
 as the faithful replication of DNA...


          Development - pre-programmed unfurling of an organism’s genomic DNA;
                                             it is what underlies the growth of all organisms...

Reasons why we should...   Study CMB :
n   It is a Core Knowledge Area of Biology...
            ... is needed to understand the CELL as the unit of life,
            ... to learn those properties common to ALL eukaryotic cells.
            by some  guesstimates : 
                    between 2 million & 100 million different species of organisms;
                    and each species has many different  types of cells...
                         adult human body has some 210 distinct cell types
                        with some 60 trillion total cells...
             CMB asks... what do all these cells have in common...
                      the answer   =  "their molecules & chemical reactivity"
                      which we need to understand to see how life works.

  What cells types will we be looking at?     [see pg 25 - 28]*
                                                                                                                 [a review of Prokaryote, Eukaryote, & Virus]
  µ Model Organisms*   cheap, plentiful, prolific reproducers, with simple genome
       and common attributes & unique properties for practical research analysis:
cell & molecular biology's research model organisms include:
          Bacteriophages - a virus that infects bacteria; today used as cloning vectors
Escheriichia coli - bacteria
 common to the human colon; molecular work horse    [database] 
          Giardia -  a primitive eukaryotic cell, an anaerobic protozoan cell with 2 nuclei [Giardiasis]
                         other eukaryotic models include:
             single celled -  Saccharomyces cerevisiae - yeast     [ pic ]
                           plants - mustard plants Arabidopsis  thaliana          [ pic ]
                      nematode - Caenorhabditis elegans                          [ 2002 Nobel ]
     animals - fruit fly Drosophilia melangaster
[Mickey] mouse - Mus musculus - common house mouse  &  its genome
          Single cell culture models
         model systems for genetic & embryonic development research grown in the lab...
Hela cells (pic + pic) -   (George & Margaret
Gey at JHU
fibroblast       (connective tissue cells easily grown in tissue culture)
                    immortal stem cells       (Stem Cell Journal   -   Stem Cell fraud)


 So then, how do you describe... 
 What is Cell and Molecular Biology - a text description*

  Is the CELL an independently functioning unit?
  Is the ORGANISM (plant or animal) more than an assembly of individual cells?
 CMB is interdisciplinary: a little bit of this, of that, and some of that, & includes...
     Cell Physiology - takes a comparative approach;  adaptations to habitats via an
                    evolutionary base...
   it asks how cells answer universal problems such as:
                                                 water conservation,  cell communication, etc.…
     Systemic Physiology -  organism or organ systems, form & function...
                                                                  insect, plant, fish, kidney, etc...physiology
     Biochemistry -  chemical & physical commonality of mechanisms of cell reactions...
glycolysis, Krebs, ETC, & ATP synthase, etc...
        Molecular Biology -  properties of organisms through structure of its molecules...
                                                    carbs, lipids, proteins, nucleic acids, etc...



 CMB  may be described as... 

   Cell & Molecular Biology is about energy & reactivity, movement & change, action & reaction;
 almost everything that happens in life (happens in cells)...
   may boil down to

   CMB replaces  the gross anatomy and physiological studies of the 17th & 18th century,
                                   with the biology of molecules & molecular systems
a 21st century.

    but as Erwin Chargaff  (former Chair of Bioc @ Columbia U; pic  Heineken Prize winner) has said,

                               " CMB...   is the practice of Biochemistry without a license "  

                                             The GOAL of modern Cell & Molecular Biology, then
                                              is to
interpret the (questions) properties of organisms 
                                              through the
structure of their constituent molecules.
   end - next lecture


















On Dec. 3, 1967 Dr. Christian Bernard - of  Cape Town, South Africa, using techniques pioneered at Stanford University by Drs. Norman Shumway and Richard Lower, performed the first successful heart transplant at Groote Schuur Hospital."

          The patient, Louis Washkansky, lived 18 days and died of a lung infection.