CHEMISTRY IN BIOLOGICAL SYSTEMS
ITS COLOR, ODOR, TASTE, AND VOLUME, AS WELL AS ANALYSES BASED ON THE PRESENCE OF PARTICULATE MATTER, TURBIDITY SEDIMENTS, BLOOD, OR PUS WERE PRACTICED IN GREEK AND ROMAN MEDICINE OF ANCIENT ANTIQUITY, AS INSTRUCTED IN THE WRITINGS OF THE HIPPOCRATIC CORPUS (HIPPOCRATES OF COS, 460–CA 370 B C ), THE MEDICAL ENCYCLO- PEDIA, DE MEDICINA OF AULUS CORNELIUS CELSUS (25 B C –CA 50 A D ) AND THE MEDICAL WORKS GALENIC CORPORUS OF GALEN OF PERGAMUM (129–210/217 A D ), THE ROMAN PHYSICIAN WHOSE THEORIES DOMINATED WESTERN MEDICINE FOR OVER A MILLENNIUM THUS, A BROWNISH TINT TO URINE WOULD BE TAKEN AS AN INDICATOR OF JAUNDICE SUCH DIAGNOSES ALONG WITH THOSE BASED ON HIPPOCRATES’ FOUR ANCIENT HUMORS OF HUMAN HEALTH (YELLOW BILE, BLACK BILE, BLOOD, AND PHLEGM) WERE THE ROOT OF GALEN’S TEM- PERAMENT THEORY (THE READER IS ENCOURAGED TO VISIT HEINZ FALK’S (15) EXCELLENT, SUCCINCT HISTORICAL SUMMARY OF THE BILE PIGMENTS AND BILIRUBIN FROM THE EARLY EGYPTIAN DYNASTIES TO THE SCIENTIFIC INVESTIGATIONS OF BILIRUBIN IN THE EARLY 19TH CENTURY THROUGH THE 1980S ) MEDICINE, SUCH AS IT WAS, OVERLAPPED WITH A TECHNIQUE (DISTILLATION) IN CLASSICAL ANTIQUITY WHEN ALCHEMY, REPRESENTING “AN AMALGAMATION OF CERTAIN CHEMICAL TECH- NOLOGIES AND PHILOSOPHICAL SPECULATIONS BEGAN TO BE A FORMAL DISCIPLINE TOWARD THE END OF THE FIRST CENTURY OF THE CHRISTIAN ERA” (22) DISTILLATES OF PLANT AND ANIMAL MATERIALS SERVED AS PHARMACEUTICALS; ALCOHOL AND HERBAL DISTILLATES ASSUMED MEDICI- NAL VALUE, THUS ASSOCIATING MIXTURES OF CHEMICAL SUBSTANCES WITH MEDICINE ALTHOUGH VISUAL DIAGNOSES BASED ON URINE AND BLOOD HAVE NOT LOST THEIR IMPORTANCE IN MODERN MEDICINE, IN THE 16TH CENTURY THE WORLD OF ALCHEMY INTRUDED INTO THE STAGNATING MEDICAL THEORY AND PRACTICE OF ANTIQUITY AND STIMULATED INVESTIGATIONS AND EXPLANATIONS OF BODILY FUNCTIONS AND DISEASES IN CHEMICAL TERMS (23) THUS, THE FAMOUS SWISS PHYSICIAN/ALCHEMIST PARACELSUS (PHILIPPUS AUREOLUS THEOPHRASTUS BOMBASTUS VON HOHENHEIM, 1493–1541), WHO BELIEVED THAT THE REAL PURPOSE OF ALCHEMY WAS TO PRODUCE MEDICINES, INTRODUCED IATROCHEMISTRY, OR CHEMISTRY IN THE SERVICE OF MEDICINE PRIMITIVE MEDICINALS AND MINERAL DRUGS WERE INTRODUCED, AND BODILY FLUIDS AND THEIR CONTENTS BEGAN TO BE PROBED AND ANALYZED BY THE USE OF THE DEVELOPING CHEMICAL METHODOLOGY AND THEN-AVAILABLE CHEMICALS AS A “MODERN” CHEMIST, IMAGINE TRYING TO INVESTIGATE CHEMICAL STRUCTURE ABSENT A KNOWLEDGE OF ANY ORGANIC CHEMISTRY, CHROMATOGRAPHY OR SPECTROSCOPY, ACQUAINTED ONLY WITH THE MOST PRIMITIVE SEPARATION METHODS AND POSSESSING NO MEANS OF ASSUR- ING A HIGH LEVEL OF SAMPLE HOMOGENEITY, YET EMBARKING ON AN INVESTIGATION OF THE PIGMENTS OF BILE AND BLOOD TO LEARN OF THEIR CHARACTERISTICS BY THE END OF THE 18TH CENTURY, SYSTEMATIC PROCEDURES FOR SEPARATING (DISTILLATION; CRYSTALLIZATION) AND IDEN- TIFYING PHYSICAL SUBSTANCES BY THEIR PHYSICAL CHARACTERISTICS AND CHEMICAL REACTIONS WERE BEING DISCOVERED AND SYSTEMATIZED THUS, THE FLUIDS OF THE BODY COULD BE PROBED BY THESE NEWLY AVAILABLE MEANS, INCLUDING COLOR CHANGES THAT MIGHT OCCUR UPON THE ADDITION OF A CHEMICAL, SUCH AS A MINERAL ACID OR ALCOHOL BIOLOGICAL FLUIDS SUCH AS BLOOD AND URINE WERE DISTILLED OF THEIR VOLATILE SUBSTANCES, AND THE DISTILLATES AND THE RESIDUES LEFT BEHIND WERE INDEPENDENTLY PROBED YET, EVEN BY THE MIDDLE OF THE 18TH CENTURY THERE WERE ONLY TWO RECOGNIZED STATES OF MATTER (LIQUID AND SOLID), AND THERE APPEARED TO BE NO CONCEPT OF MATTER IN A GASEOUS STATE NOR WERE THERE CRITERIA FOR PURITY AND METHODOLOGIES FOR ASCERTAINING IT THE SITUATION WAS TO CHEMISTRY IS THE LOGIC OF BIOLOGICAL PHENOMENA YEARS (22) TO THE PRE-SOCRATIC GREEK PHILOSOPHERS LEUCIPPUS AND DEMOCRITUS, WHO SPECULATED THAT EVERYTHING IS COMPOSED OF EXTREMELY SMALL PARTICLES, WHICH THEY CALLED ATOMS, OF WHICH THERE ARE MANY DIFFERENT KINDS, DISTINCT IN SHAPE, SIZE, CHEMISTRY IS THE LOGIC OF BIOLOGICAL PHENOMENA AND WEIGHT, PHYSICALLY BUT NOT GEOMETRICALLY INDESTRUCTABLE ATOMS WERE SAID TO MOVE AT RANDOM, ABLE TO COLLIDE AND INTERLOCK TO FORM CLUSTERS THAT ARE THE BASIS FOR THE OBJECTS OF OUR PERCEPTION SUCH CLUSTERS COULD DISINTEGRATE INTO ATOMS AND AGAIN REFORM DIFFERENTLY THE BASIS OF CHEMICAL ATOMISM AND THE THEORY OF ATOMIC WEIGHTS OF ELEMENTS GO BACK ONLY 200 YEARS TO JOHN DALTON (1766–1844) THE CONCEPT OF A CHEMICAL STRUCTURE IS RELATIVELY MORE RECENT, AND WHAT CONSTITUTES A CHEMICAL STRUCTURE EMERGED THROUGH MANY STAGES OF EVOLUTION THUS, LATE IN THE 19TH CENTURY, UNTIL EARLY IN THE 20TH, INFLUENTIAL MAINSTREAM SCIENTISTS SUCH AS WILHELM OSTWALD (1853–1932, 1909 NOBEL PRIZE IN CHEMISTRY) DID NOT BELIEVE IN ATOMS HE SPOKE FEROCIOUSLY AGAINST THEM; YET IN 1906 HE WAS FORCED TO CAPITULATE ON THE BASIS OF PERRIN’S DATA (JEAN BAPTISTE PERRIN, 1870–1942, 1926 NOBEL PRIZE IN PHYSICS) THAT CONFIRMED EINSTEIN’S 1905 THEORY OF BROWNIAN MOTION (ALBERT EINSTEIN, 1879–1955, 1921 NOBEL PRIZE IN PHYSICS) BY EMPIRICALLY CALCULATING AVOGADRO’S CONSTANT, CONCLUSIVELY PROVING DALTON’S ATOMIC THEORY THE EMER- GENCE OF ORGANIC CHEMISTRY IN THE 19TH CENTURY FOCUSED ON SCIENTIFIC INVESTIGA- TIONS OF SUBSTANCES FOUND IN NATURE THAT COULD BE DETECTED BY THE SENSES, ESPECIALLY BY THEIR ODORS AND COLORS – ESPECIALLY COLORS THAT WERE DISTINCT AND HIGHLY VISIBLE THE EARLY “ORGANIC” CHEMISTS WERE TYPICALLY ALSO PHYSICIANS AND THUS UNSURPRIS- INGLY THEIR CURIOSITY WAS PIQUED BY THE “PIGMENTS OF LIFE”: THE RED PIGMENT OF BLOOD AND THE YELLOW PIGMENT OF BILE, AND THAT MOST NOTICEABLE TO ALMOST ALL, THE GREEN PIGMENT OF PLANTS THESE WE NOW KNOWN AS HEME, BILIRUBIN AND CHLOROPHYLL, RESPECTIVELY (FIG 1 1) NOR IS IT SURPRISING, GIVEN THEIR STRUCTURAL COMPLEXITY, THAT ELUCIDATION OF STRUCTURE CONSUMED THE EARLY DECADES OF THE PAST CENTURY IN WHICH THE NOTION OF A MOLECULE AND STRUCTURAL ORGANIC CHEMISTRY WAS IN ITS INFANCY THE IMPORTANCE OF SUCH PIGMENTS WAS RECOGNIZED BY NOBEL PRIZE AWARDS IN (RICHARD MARTIN WILLSTÄTTER, 1872–1942, FOR PLANT PIGMENTS, ESPECIALLY CHLORO- PHYLL), 1930 (HANS FISCHER, 1881–1945, FOR HEMIN AND CHLOROPHYLL), (ROBERT BURNS WOODWARD, 1917–1979, FOR ORGANIC SYNTHESIS, INCLUDING CHLORO- PHYLL), 1988 (JOHANN DEISENHOFER, ROBERT HUBER, AND MICHEL HARTMUT, FOR THE DETERMINATION OF THE THREE-DIMENSIONAL STRUCTURE OF A PHOTOSYNTHETIC REACTION CENTER, BACTERIOCHLOROPHYLL AND CYTOCHROME) A HEME CHLOROPHYLL A BILIRUBIN (Z ) (Z ) (Z ) (Z ) (Z ) H H H H BILIVERDIN H H H 8 HO2C CO2H N N N N FE HO2C CO2H N N O N N O H H HO2C CO2H N N O N N O H HO2C CO2PHYTYL N N N N MG O FIG 1 1 THE PIGMENTS OF BLOOD (LEFT), BILE (MIDDLE), AND GREEN LEAVES (RIGHT) CHEMISTRY IS THE LOGIC OF BIOLOGICAL PHENOMENA