SCIENTIFIC THINKING M N EL-Bolkainy · (Biotechnology revolution) THE SCIENTIFIC REVOLUTION ......
Transcript of SCIENTIFIC THINKING M N EL-Bolkainy · (Biotechnology revolution) THE SCIENTIFIC REVOLUTION ......
SCIENTIFIC THINKING
Part II
Scientific Era (1600 AD – 2000 AD)
M N EL-Bolkainy
2013
OBJECTIVES
A The Search for a Method
(Scientific revolution)
B The Search for Etiology & Mechanisms 1. Gross pathology
2. Epidemiology
3. Microscopic pathology
4. Molecular pathology
(Biotechnology revolution)
THE SCIENTIFIC REVOLUTION
(1650 – 1800)
AIM To replace the historic approach of
gaining knowledge based on speculation by a more rational objective method
THE PIONEER FOUNDERS
Galileo Galilei
Italy
(1564-1642)
Francis Bacon
England
(1561-1626)
Rene Descartes
France
(1596-1650)
THE ADVANCEMENT OF LEARNING
(Bacon, 1605)
THE VISION
• Science and technology could transform the world to the better
• Science placed in unworthy (irresponsible) hands could be destructive
• Young scientists are more creative than old ones
THE TWO WORLD SYSTEMS
(GALILEO, 1623)
ACADEMIC FREEDOM
The first to revolt against dogmatism by
supporting the heliocentric theory
QUANTITATION OF OBSERVATIONS
Hence allowing mathematical analysis
DISCOURSE ON METHOD
(Descartes, 1637)
SKEPTICISM
• We start by doubt (hypothesis) in order to reach truth (conclusion)
• The only reliable knowledge is mathematics
• Except for God and Soul, the whole universe is mathematical
• The aim of science is to control nature
THE STEPS OF SCIENTIFIC METHOD
1. Definition of a problem
2. Collect data (observations)
3. Formulate a hypothesis
4. Test hypothesis (experiment)
5. Draw conclusions
6. Publication of results
7. Reproducibility by others
RESEARCH ERRORS
SAMPLE Selected sample
Few cases
METHODS Outdated reagents
Equipment error
Personal error
Statistical mischoice
CONCLUSION Invalidity
Causality error
THE TREE OF LIVE Association or Causal Relation ?
Medieval concept
of genesis of
Animals from plants
CRITERIA OF CAUSALITY
1. Strong association
2. Direct relation
3. Temporal relation
4. Explanatory mechanism
IMPORTANT QUESTION • Can we gain knowledge without
applying the scientific method ?
ANSWER: YES 1. If experiment is impossible (Darwin theory of evolution) 2. Scientific discovery by chance
EVOLUTION BY NATURAL SELECTION AND SURVIVAL OF THE MOST FIT
Charles Darwin
(1809 – 1882)
Birds of same species
have different peaks in
different habitats
THE DURATION OF DARWIN RESEARCH (1809 – 1882)
Step Years
Observations (Beagle tour) Formulation of theory (Inductive reasoning) Publications: 1. The origin of species ( 1859) 2. Descent of man (1971)
5
22
13
Total 40
THE BROAD APPLICABILITY OF DARWIN THEORY
Natural Science
Evolution of Species
Bacterial resistant strains
Cancer cell progression
Social Science
Religious, colonial,
class and ideological struggle
THE FUTURE OF SOCIAL STRUGGLE
1. END OF HISTORY
(Francis Fukuyama, 1992)
2. CLASH OF CIVILIZATIONS
(Samuel Huntington, 1996)
Judeo – Christian against Islam
The west against the reset
3. DIALOGUE AMONG CIVILZATIONS (Mohamed khatami, 2000)
THE GENETIC CONFIRMATION OF DARWIN THEORY
1. Discovery of chromosomes,
(Wilhelm Hofmeister, 1848)
2. Laws of heredity,
(Gregor Mendel, 1866)
3. Reproduction of Mendel laws,
(Hugo de Vries et al, 1900)
4. Mutation in Drosophila,
(Thomas Morgan, 1919)
5. Discovery of genes
(Walter Fiers, 1972)
MUTATIONS IN DROSOPHILA (Thomas Morgan, 1919)
Differences in eye color
and length of wings
SCIENTIFIC DISCOVERIES BY CHANCE
1. Ovary – breast hormonal relation,
(Sir George Beatson, 1896)
2. Radioactivity of uranium,
(Antoine Becquerel, 1896)
3. Penicillin, the first antibiotic,
(Alexander Fleming, 1928)
4. Cancer Chemotherapy (Mustard gas, 1943)
(Gilman et al, 1946)
THE SEARCH FOR THE CAUSE AND
MECHANISM OF DISEASE
18th cent Gross Pathology (Morgagni, 1761)
18th cent Epidemiology (Pott, 1775)
19th cent Cellular Pathology (Virchow, 1858)
20th cent Molecular Pathology (Multiple authors, 1950 – 2013)
“Clinicopathological
Correlation of 700 Autopsies”
GIOVANNI BATISTA
MORGAGNI
(1682 – 1771)
SEATS AND CAUSES
OF DISEASES, 1761
EPIDEMIOLOGY REVEALS ETIOLOGY AND ALLOWS PREVENTION
ETIOLOGY Scrotal Cancer is common among chimney sweepers (Sir Percival Pott, 1775)
PREVENTION Legislation to ban this occupation
ASBESTOS AND MESOTHELIOMA IN USA
Fabricated Research Delayed Banning 29 Years
1. Mesothelioma is related to asbestos
exposure (J. Eagner 1960)
2. Industry – Supported fabricated research to prove otherwise
3. Carcinogenic risk firmly established (Roggli, 1987)
4. Production of asbestos was finally banned in USA (1989), but, continued in developing countries
TOBACCO SMOKING & LUNG CANCER IN USA Money Talks / Thanks to Clever Lawyers
1. Smoking is related to
lung cancer
(Wynder,Doll,1950)
2. Lawsuit in USA against tobacco industry
3. Billions of dollars compensation but production continues
VAN GOGH, 1886
LIGHT MICROSCOPY The Most Important Technology
of the 19th Century
THE INVENTION OF MICROSCOPE
EARLY INVENTORS 1. Compound microscope
(Galileo, 1610)
2. Simple microscope
(Leeuwenhoek, 1721)
MASS PRODUCTION (Ernest Abbee,
Carl Ziess, 1900)
CONTRIBUTIONS
OF LIGHT MICROSCOPY
1. The cell theory (Schwan & Schleiden
1838)
2. Bacteriology (Ferdinand Cohn, 1853)
3. Cell Pathology (Muller & Virchow, 1858)
4. Cell division (W. Flemming, 1882)
5. Microsurgery (Carl Nylen, 1921)
6. Laser microsurgery (Strong & Jako, 1972)
CONTRIBUTIONS OF LIGHT MICROSCOPY
(Continued)
7. Phase Contrast (First Zernike, 1932)
8. Cytophotometry (T. Casperson, 1936)
9. Immunohistology (A. Coons, 1942)
10. Cytogentics (Tjio & Levan, 1956)
11. Molecular Genetics (Langer- Safer,1982)
12. Laser Capture Micro dissection, LCM
(Emmert – Buck, 1996)
• Cells are the units of disease
• Microscopic studies are more precise than gross examination
RUDOLF VIRCHOW
(1821 – 1902)
CELLULAR PATHOLOGY
1858
THE BIOTECHNOLOGY
REVOLUTION
(1950 – 2013)
AIM To study biological phenomena at
molecular level, thus, revealing mechanisms and allowing the application of targeted therapy
THE FOUNDATIONS AND
PREREQUISITES OF
BITOTECHNOLOGY REVOLUTION
1. Well-trained staff
2. Team work (multidisciplinary)
3. Efficient equipments
4. Research funds
NATIONALITY OF 32 NOBEL PRIZEWINNERS IN BIOTECNOLOGY (1950 – 2013)
American 15
British 4
French 4
German 3
Swiss 1
Australia 1
India 1
Japan 1
Egypt 1
Israel 1
RESEARCH SPENDING BY COUNTRIES (Billions of US Dollars per year)
USA 405 India 40
China 297 Russa 30
Japan 160 Israel 9
Germany 70 Egypt 1
(Wikipedia, 2011)
NB Figures included military spending
TECHNOLOGY INSTITUTES BY COUNTRIES
USA 28 India 16
China 11 Russa 9
Japan 6 Israel 2
Germany 17 Egypt 2
(Wikipedia, 2013)
BIOTECHNOLOGY NOBEL PRIZES ARRANGED BY SUBJECT
No
Genomics 8
Proteomics 11
Infections and Cancer 5
Laser 2
Total 26
MOLECULAR SRUCTURE OF DNA
James Watson
(American)
Francis Crick
Maurice Wilkins (British)
1962
DNA
MOLECULAR STRUCTURE & DOUBLE HELIX MODULE
ORGANIZATION PACKAGE OF DNA TO NUCLEOSOMES AND CHROMOSOMS
THE BILOGIC DOGMA
DNA
mRNA
Protein
GENE REGULATION 1962 Francis Jacob & Jaques Monod Activator and suppressors in E. Coli 2006 Roger Kornberg RNA polymerase and nucleosome 2006 Anderw Fire Epigenetic m-RNA silencing 2009 Elizabeth Blackburn Telomerase
REGULATOR GENES MODEL
Activator
Suppressor
Re
gu
lato
r G
en
es
EPIGENETIC GENE CONTROL
“A change of gene expression
apart from mutation or the conventional regulator gene model”
CHROMATIN REMODELING BY HISTONE ACETYLATION
Packed nucleosomes
(Silent genes)
Dissociated nucleosomes
(Active genes)
CYTOSINE METHYLATION
m-RNA SILENCING
POLYMERASE CHAIN REACTION
(PCR)
Kary Mullis
(American)
1993
PCR
A segment
of DNA is amplified to a million in
20 cycles
RESTRICTION ENDONUCLEASES GENETIC ENGINEERING
Weber Arber (Swiss)
1978
GENETIC ENGINEERING IN VITRO
Restriction Endonucleases Diagnostic Probes
TARGETING GENES TO CHANGE PHENOTYPE (Genetic Engineering in Vivo) 2007 Mario Capeechi Transfer of a gene to replace its
homologous gene in embryonic stem cells (Knockout mice)
2012 John Gurdon & Shinya Yamanaka Conversion of mature cell to a stem cell (Genetic reprogramming) applied in (Frog, Cheep, Mice and
Humane)
PROTEIN STRUCTURE
TRANSLATION, MODIFICATIONS, TRANSPORT AND DEGRADATION
2009 Venkatraman Ramakrishnan Ribosome and protein synthesis 2013 James Rothman Intracellular vesicle transport 2004 Aaron Ciechanover Ubiquitin – Proteasome pathway (UPP) of protein degradation.
PROINSULIN
Translation,
Modification,
And transport
THE BILOGIC PARADOX
DNA (25,000 Genes) mRNA
Protein (1000,000 Proteins)
EXPLANATION
1- One gene produces multiple proteins
2- One protein has different activities through
modifications
UBIQUITIN- PROTEASOME PROTEIN DEGRADATION
SIGNAL TRANSDUCTION
1999 Gunter Blobel Protein Signaling 2012 Brain Kobilka G- protein – coupled receptors
SIGNAL TRANSDUCTION
CELL CYCLE CONTROL Discovery of Cyclin Genes in Yeasts
Leland Hartwell
(American)
2001
CELL DIVISION CYCLE (cdc) CONTROL
IMMUNOLOGY 1972 Gerald Edelman Structure of antibodies 1980 Baruj Benacerrof Major histocompatibility complex (MHC) 1984 Georges Kohler The hybridoma technology 1984 Neils Jerne Lymphocyte clonal selection 2011 Bruce Beutler Innate immunity (Dendritic Cells)
THE STRUCTURE OF ANTIBODIES
THE HYBRIDOMA
TECHNOLOGY
“The evil is used
to produce the good”
CLONAL SELECTION OF B- LYMPHOCYTES
First encounter
(memory cells)
Second encounter
(Clonal expansion)
ANTIGEN PRESENTATION TO T-LYMPHOCYTES IN ASSOCIATION WITH (MHC)
INFECTIONS AND CANCER 1966 Francis Rous First virus-induced tumar 1974 David Baltimore Retrovirus oncogenesis (in vitro) 2005 Barry Marshall H. pylori and gastric cancer 2008 Harold Hausen HPV and Cervical Cancer 2008 Luc Montagnier & Francois Bane-Sinoussi HIV Discovery (AIDS)
ROUS RETROVIRUS-INDUCED SARCOMA IN CHICKENS
LASER BEAM DISCOVERY
Charles Towns
(American)
1964
The most important technology of
the 20th Century
GENERATION OF LASER BEAM
(Chromium)
PROPERTIES OF LASER BEAM
Single wave, coherent, parallel
Monochromatic, high energy, long distance
REGULAR LIGHT
APPLICATIONS OF LASER
Computers Industry Medicine Show Light
Barcodes Lunar Distance Military Biology
APPLICATION OF LASER IN BIOLOGY
1. Flow cytometry (W.H. Coulter, 1953)
2. Flow fluorescent microscopy (W. Gohde, 1968)
3. Laser capture micro dissection, LCM (E. Buck, 1995)
4. Photo thermal effect of laser on gold nano particles (M. El – Sayed, 2006)
5. Dynamics of molecular reactions femtochemistry
(A. Zewail, 2009)
FLOW CYTO PHOTO METRY
Rapid multi-parameter
Analysis of thousands
of cells
LASER CAPTURE MICRODISSECTION isolation of individual cells for study
FEMTOCHEMISTRY DYNAMICS USING ULTRAFAST LASER
1999 Ahmed Zewail
• The Academic Discovery (1990)
(Femtosecond = 0.000,000,000,000,001)
• The Technologic application (2009)
(The 4-Dimentional EM)
“Technology determines
the power of nations,
not natural resources,
population size or ideology”