Lessons Learned: Milestones of Toxicology

Steven G. Gilbert
1
and Antoinette Hayes
2
1
Institute of Neurotoxicology and Neurological Disorders and
2
Northeastern University
Contact information: Steven G. Gilbert at sgilbert@innd.org For more information, its interactive (clickable) at www.asmalldoseof.org 2006 Steven G. Gilbert
Antiquity
3000 BCE 90 CE
Shen Nung
2696 BCE
TheFather of
Chinese
medicine, noted
for tasting 365 herbs and
said to havedied of atoxic
overdose.
Ebers Papyrus
1500 BCE
Egyptianrecords
contains 110
pages onanatomy
andphysiology, toxicology,
spells, andtreatment,
recordedonpapyrus.
Gula 1400 BCE
Sumerian texts refer to a
femaledeity, Gula. This
mythological figurewas
associated with charms,
spells and poisons.
Homer
850 BCE
Wroteof the
useof arrows
poisoned with venomin the
epic taleof The Odyssey
and The Iliad. FromGreek
toxikon arrow poison.
Socrates
(470-399 BCE)
Charged with
religious heresy
and corrupting themorals
of local youth. Death by
Hemlock - activechemical
alkaloid coniine.
Hippocrates
(460-377 BCE)
Greek physician,
observational
approach to human disease
and treatment, founder of
modern medicine, named
cancer after creeping crab.
Mithridates VI
(131-63 BCE)
Tested antidotes
to poisons on
himself and used prisoners
as guineapigs. Created
mixtures of substances
leading to termmithridatic.
L. Cornelius Sulla
82 BCE
Lex Cornelia de
sicariis et
veneficis law
against poisoning peopleor
prisoners; could not buy,
sell or possess poisons.
Cleopatra
(69-30 BCE)
Experimented
with strychnine
and other poisons on
prisoners and poor.
Committed suicidewith
Egyptian Asp.
Pedanius
Dioscorides
(40-90 CE)
Greek
pharmacologist and
Physician,wroteDe Materia
Medica basis for the
modern pharmacopeia.
Mount Vesuvius
Erupted August 24
th
79 CE
City of Pompeii &
Herculaneum
destroyed and buried
by ash. Pliny theElder
suffocated by volcanic gases.
Middle Ages
476 CE 1453
Greek Fire
673 CE
Ancient
napalm described by the
Crusaders as consisting of
naptha, quicklime, sulphur,
& saltpeter.
Ergot Outbreak
994 CE
40,000 died
fromeating
contaminated wheat/rye
caused gangrene- known as
St. Anthonys Fire.
Moses Maimonides
(1135-1204)
J ewish
philosopher &
physician wrote:
Treatise on Poisons and
Their Antidotes.
Albertus Magnus
(1193-1280)
Dominican friar
wroteextensively
on compatibility
religion and scienceand
isolated arsenic in 1250.
Raymundus Lullius
1275
Ether discovered
by Spanish
chemist and
later called
sweet vitriol.
Knights Templars
(1118-1307)
Christian military
order alleged to
beexperts with
poisons. They searched for
theElixir of Life.
Petrus de Abano
(1250-1315)
Italian scholar
translated
Hippocrates and
Galen to Latin. Wrotebook
on poisons: De Venenis.
The Black Death
(1347-1351)
Bubonic &
pneumonic
plagueravaged Europe
leaving thehighest number
of casualties in history.
Venetian Council of
Ten - 1419
Group of
peoplewho
carried out
murders with poison for a
fee.
Zhou Man
1423
Chineseexplorer
lost 1000s of crew
members fromuranium
exposurewhilemining lead
in J abiruAustralia.
Rodrigo &
Cesare Borgia
(1400-1500)
Poisoned many peoplein Italy
for political and monetary gain.
Used arsenic in aconcoction
called LaCantrella.
Renaissance
14th16th
Centuries
Leonardo de Vinci
(1452-1519)
Experimentedwith
bioaccumulationof
poisons inanimals
andcalledthe procedure
passages.
Pope Clement VII
(1478-1534)
Died (possibly
murdered) after
eating amanita
Phalloides, (death cap)
mushroom.
Paracelsus
(1493-1541)
All substances
arepoisons;
thereisnonewhichisnot a
poison. Theright dose
differentiatesapoisonfroma
remedy.
Georgius Agricola
(1494-1555)
WroteDe Re
Metallica published
1556. Themost
comprehensivebook on
miningandmetallurgy.
Catherine Medici
(1519-1589)
Queen of France,
expert assassin,
tested poisons
on thepoor and
thesick.
William Piso
1640
In Brazil,
studied effects
of Cephaelis
Ipecacuanha,
an emetic; treat dysentery.
Shakespeare
(1564-1616)
FromRomeo &
J uliet - act 5
Heres to my love! O true
apothecary! Thy drugs are
quick. Thus with akiss I die.
Hieronyma Spara
~1659
Roman women &
fortuneteller
organizedwealthy wives and
sold themaarsenic elixir to
murder their husbands.
Catherine Monvoisin
(LaVoisin)
(1640-1680)
Accusedsorcerer
andconvicted
poisoner inFrance.
Shewasburnedat thestake.
Guilia Tophania
(1635-1719)
Italian woman who
supplied poison (arsenic) to
wives looking to murder
their husbands. Later
executed by strangulation.
King Louis XIV
1682
Passed royal decree
forbidding apothecaries
to sell arsenic or poisonous
substances except to persons
known to them.
1700s
Devonshire Colic
1700s
Devonshire,
England. High
incidenceof lead
colic drinking
contaminatedcider.
John Jones
1701
Englishdoctor wrote
The Mysteries of Opium
Reveald describedmany
treatments of opium, but also
withdrawal andaddiction.
Richard Meade
(1673-1754)
In1702, wroteA
Mechanical
Account of Poisons
dedicatedto poisonssnakes,
animalsandplants.
Carl Wilhelm
Scheele (1742-176)
Swedishapothecary
andchemist,
discoveredoxygen,
barium, chlorine,
manganese, and
hydrogencyanide.
Percivall Pott
(1714-1788)
Britishphysician
whorecognized
coal-tar caused
cancer of thescrotumin
chimney sweeps. Chimney
SweepersAct of 1788.
Felice Fontana
1767
Italianchemist and
physiologist who
wasthefirst tostudy
venomoussnakes. Discovered
that viper venomaffectsblood.
Freidrich Serturner
(1783-1841)
Isolatedanalkaloid
Fromopiumpoppy
in1803. Henamed
it Morphine after Morpheus, the
Greek godof dreams.
Francoise Magendie
(1783-1855)
Discoveredemetine
andstudiedeffects
of strychnine&
cyanide. Called
thefather of
experimental pharmacology.
Fowlers Solution
1786-1936
Potassiumarsenite
solutionprescribed
asageneral tonic
andusedfromabout
1786to1936. Used
by CharlesDarwin?
Pierre Ordinaire
1797-1915
Createdelixir
usingabsinthe
popularizedandsoldby Henry
Pernod. Absinthewasusedby
Vincent VanGogh; bannedin
1915, subject of Degas.
Mateu J.B. Orfila
(1787-1853)
Consideredthefather
of moderntoxicology.
In1813hepublished
Traite des Poisons,
whichdescribedthesymptomsof
poisons.
1800s
Thomas de Quincey
(1785-1859)
Englishwriter
becameaddicted
toopiuminearly
1800sand
publishedConfessions of an
Opium Eater in1821.
James Marsh
(1794-1846)
Chemist developed
andperfectedtheMarshtest for
arsenic. TheimprovedMarsh
test wasusedforensically for
thefirst timein1840duringthe
trial of MarieLafarge.
Robert Christison
(1797-1882)
Toxicologist at
University of
Edinburgh wroteTreatise on
Poisons in 1829; invented
poisonharpoon for whaling
that contained prussic acid.
Claude Bernard
(1813-1878)
French
physiologist
studiedtheeffects
of carbonmonoxideand
curare. Influencedby
FrancoiseMagendie.
Ascanio Sobrero
(1812- 1888)
Italianchemist, in
1847discovered
nitroglycerin, a
powerful explosive
andvasodilator. Alfred
Nobel was his student.
Theodore G. Wormley
(1826-1897)
Wrotethefirst
Americanbook
dedicatedto
poisons in1869
entitled: Microchemistry of
Poisons.
Joseph Caventou &
Pierre Pelletier
1820
Frenchpharmacistsisolated
quininefrombark of Cinchona
treeinback of their pharmacy.
Arsenic Act 1851
Requiredarsenic tobecolored
withsoot or indigotoprevent
accidental poisoning.
Friedrich Gaedcke
1855 Isolated
cocainefrom
Erythroxylon coca.
Louis Lewin
(1854-1929)
German
pharmacologist
studiedandclassified
hallucinogenic plants,
alcoholsandother
psychoactivecompounds.
Emil Fischer
1852-1919
Isolatedthestimulant caffeine
fromplant extractsin1895.
Constantine Fahlberg
Saccharin - 1879
ConstantineFahlberg
discoveredsaccharin
whileworkinginthe
laboratory of Ira
Remsen(right)
in1879.
1900-1930s
Upton Sinclair
(1878-1968)
Published
The Jungle
in1905.
Chronicledtheunsanitary
conditionsinmeat packing
industry inChicago.
Pure Food and
Drugs Act - 1906
HarveyWashington
Wiley, M.D. (1844-
1930). Law prevents
productionor trafficking
of mislabeled, adulterated
or poisonousfoods, drugs,
medicines, andliquors.
Chemical Warfare A
Reality 1915
German
chemist Fritz
Haber (1868-1934)
developedblisteringagents
usedinWWI; chlorineand
cyanidegases.
U.S. Prohibition
1919-1933
Law that made
theproduction
andsaleof
alcoholic beverages
illegal but very profitable.
Geneva Protocol
1925
Banneduseof
chemical weapons.
Updatedin1993
astheChemical Weapons
Convention to include
banningproduction.
Ginger Jake 1929
Alcoholic tonic produced
illegally duringprohibition
adulteratedwithTOCP
producedOPIDN
(J akeLeg),
affecting50,000
adults.
Hawk's Nest
Incident 1927-1935
Hundredsof black
workersdiefrom
acutesilicosiswhile
diggingtunnel for a
hydroelectric project
for UnionCarbide.
Gerhard Schrader
(1903-1990)
GermanChemist
accidentally
madenerveagents; sarin, tabun,
soman, andcyclosarinwhile
developinginsecticides1938;
agentsusedinWWII.
Elixir Sulfanilamide
1937
Food Drug &
Cosmetic Act
1938
100die, diethylene
glycol asavehicle.
Albert Hofmann
1938
Lysergic acid
(LSD) synthesized
intheSandoz
Laboratory (now
Novartis). In1943Hoffman
testedLSD onhimself.
Marijuana Tax Act
1937
Federal criminal
offensetopossess,
produce, or dispense
hemp. Non-medical
useprohibitedinCalifornia(1915)
andTexas(1919).
1940-1960s
DDT 1939
Recognized as
insecticideby theSwiss
scientist Paul Hermann
Mller, who was awarded
the1948 Nobel
Prizein Physiology
and Medicine.
Banned in 1972.
2,4-D 1946
Developed during
WW II at British
Rothamsted
Experimental
Station, by J .H. Quastela
and sold commercially in
1946. Used to control
broadleaf plants.
Minimata Japan
(1950s)
MinimataBay
contaminated
withmercury by chemical
industry. Thousands adults
andchildrenwerepoisoned
fromeatingfishcontaminated
withmethyl mercury.
Poison Control
Centers 1953
First, Chicago
1953, second
at Duke
University,
NC in 1954, and third
opened in Boston 1955.
Journal of Tox. &
App. Pharmacology
1959
Adopted by
SOT until 1981
when SOT
founded Fundamentals of
Applied Toxicology.
Thalidomide
(1959-1960s)
Drugprescribed
to pregnant womenfor
morningsickness induced
birthdefects.
Frances Kelsey
of FDA blocked
approval inU.S.
Society of Toxicology
1961
Founded
March 4, 1961,
first formal
meeting held April 15, 1962
(9 founders, 183
charter members).
Alice Hamilton
(1869-1970)
Pathologist and
first femalefaculty
member at Harvard
Medical School. Associated
worksitechemical hazards
withdisease. Studiedeffects
of lead& rubber onworkers.
Rachel Carson
(1907-1964)
Scientist lead
crusadeagainst theuseof
dichlorodiphenyltrichloroethane
(DDT) apesticideand
persistent organic pollutant.
Carsonseveral booksincluding
Silent Spring published1962.
Occupational Safety
& Health Act 1970
Act passed on December
29, 1970 to ensureevery
worker asafeand healthful
workplace.
U.S. EPA
1970
Established to
consolidatefederal research, on
monitoring, standard-setting
and enforcement activities to
ensurehuman & environmental
protection.
1970-2006
Mr. Yuk
1971
Symbol adopted
by thePittsburghPoison
Center at TheChildrens
Hospital in1971. Usedto
educatechildrenandparents
about poisons andto prevent
accidental poisonings.
Iraq Mercury
1971
Pink-
colored
seed grain coated with a
mercury fungicidewas
tragically consumed by
Iraqis tragically affecting
over 40,000 people.
Bangladeshi 1970s
Arsenic poisoning
Tubewells,
drilled to
provideclean
drinking water, are
contaminated by arsenic
resulting in millions of
peopleharmed.
First Modern
Toxicology
Textbook
1975
Louis J . Casarett
& J ohn Doull edited,
Toxicology: The Basic
Science of Poisons, in 1975.
Love Canal Disaster
1978
August 7, 1978
US President
J immy Carter
declaredLoveCanal afederal
emergency. 42millionpounds
of over 200chemicals
contaminatedLoveCanal,
disruptingmany lives.
IUTOX 1980
International Unionof
Toxicology
American Board
of Toxicology (ABT)
1979 - First examAug. 1980
Academy of
Toxicological
Sciences (ATS)
1981
Times Beach 1983
Dangerous levels of dioxin
discoveredinTimes Beach,
MO. EPA orders
thetown
evacuationand
makes it a
Superfundsite.
All residents gone
by 1985.
Bhopal Disaster
Dec. 3, 1984
Accidental release
40metric tonsof
methyl isocyanate
fromaUnion
CarbideIndianpesticideplant
inheart of city resultedinthe
killingthousands, andinjured
100sof thousands.
Chernobyl Accident
April 26, 1986
TheChernobyl
nuclear power plant
accident produceda
plumeof radioactive
debrisover the
Ukraine, Eastern
Europe, Scandinavia, UK and
easternUSA.
Tokyo Subway Sarin
Gas Attack 1995
Members of religious group
Aum
Shinrikyo
releasedsarin
gasin5places
inTokyo subway, killing
12andinjuring 6,000.
Vioxx (1999-2004)
A nonsteroidal anti-inflammatory,
COX-2selectiveinhibitor for
treatment of osteoarthritis,
producedby Merck & Co.
andvoluntarily
withdrawnbecause
of risk of heart
attack & stroke.
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Historical Milestones and Discoveries Which Shaped the Toxicology Sciences
Steven G. Gilbert
1
and Antoinette Hayes
2
1
Institute of Neurotoxicology and Neurological Disorders and
2
Northeastern University
Knowledge of the toxic and healing properties of plants, animals, and minerals has shaped civilization for millennia. The foundations of
modern toxicology are built upon the significant milestones and discoveries of serendipity and crude experimentation. Throughout the ages,
toxicological science has provided information that has shaped and guided society. This poster presentation examines the development of the
discipline of toxicology and its influence on civilization by highlighting significant milestones and discoveries related to toxicology. The
examples shed light on the beginnings of toxicology, as well as examine lessons learned and re-learned. This project is also an effort to
examine how toxicology and the toxicologist have interacted withother scientific and cultural disciplines, including religion, politics, and the
government. Toxicology has evolved to a truescientific discipline with its own dedicated scientists, educational institutes, sub-disciplines,
professional societies, and journals. It now stands as its own entity while traversing such fields as chemistry, physiology, andpharmacology.
We invite you to join us on a path of discovery and to offer your suggestions as to what are the most significant milestones anddiscoveries in
toxicology. An interactive version of the poster is available at www.asmalldoseof.org.