A long way to Science

A short history of biological thinking

Science starts from curiosity

 The emergence of biological techniques
Microscopy

Cornelis Drebbel
(1572-1633)

The ‚Edison’ of his time

The first microscope 1619 The
‚lunette de Dreubells’ Leeuwenhoek
microscope
Antonie van Leeuwenhoek
(1632-1723)

First saw
• Protists
• Bacteria (Animalcules)
• Spermatozoa
Zacharias Janssen • Muscular fibres
• Red blood cells Robert Hooke (1635-1703)
(1585-1632) Cork cells
Robert Hookes’ Micrographia from 1665
 Phase contrast microscope Electron microscope

Traditional and phase contrast images from a

phase contrast microscope (1933) by Frederyk
Zernike (1888-1966, Nobel Price in 1953)
Transmission EM Scanning EM (1937)
(1933) by Ernst Ruska by Manfred von
(1906-1988, Nobel Ardenne (1907-1997)
Price in 1986)
 Beyond the diffraction limit

Confocal light microscopy (since 1960) Super resolution light microscopy (since 1978)

Confocal laser microscopy (since 1977) Microscopes use focused laser shots
(singleton or pairs) to obtain images.
overcomes the diffraction limits of
classical microscopy (250 nm) 3D light microscopic nanosizing (LIMON)
microscopy (resolution of several nm)
Stochastic optical reconstruction microscopy
(STORM) (20 nm)

Stimulated emission
depletion (STED) microscopy uses
pairs of synchronized laser pulses Stefan Hell (1962-
Nobel Price 2014
 X-ray crystallography
• Father of geology
• Works on anatomy
Johannes Kepler (1571-1630) • Heart is a muscle
hypothesized that snowflake • Fossils (shark teeth)
symmetry was due to hexagonal are remains of
packing of ice particles living beings
Nicolas Steno
(1638-1686
Detection of X- De solido intra solidum naturaliter content
rays in 1895 First accurate description of crystall structure

Detection of X-
Wilhelm Konrad ray diffraction
Röntgen (1845-1923) by cristalls in
Nobel Price 1901 1911
Max von Laue
(1879-1960),
Nobel Price 1914
 Southern DNA and
Electrophoresis
Chromatography Northern RNA blot
(1900) (1975, 1977)

Principles developed in 1930 by Tiselius

1969 SDS gels (sodium dodecyl sulfate

polyacrylamide gel) by Osborn and Weber

1977 sequencing gels

Mikhail Tsvet Sir Edwin Arne Tiselius
(1872-1919) Southern (1938- (1902-1971
Nobel Price in
1948)

Mary Osborne
DNA microarrays (1940-)
(1995) Klaus Weber
(1936-2016)
 Protein and DNA sequencing
Robert Holley (1922-1993,
Nobel Price 1968) determined in
1965 the sequence of
alanine tRNA
from Saccharomyces cerevisiae
The Bovine insulin amino acid
sequence (1951, 1953)

Frederick Sanger Peptide end-group analysis The virus Phi X 174

(1918-2013)
First complete
Nobel Prices in 1958 First demonstration that proteins
genome by
and 1980 have a sequential structure.
Sanger’s lab in
1977

Arthur Kornberg (1918-

2007, Nobel Price 1959)
synthesized the Phi X
174 genome in 1967

The start of
synthetic biology
An early protein sequencer (since 1969)
 Neurosciences

The first electroencephalogram (1924) by Hans Berger (1873-1941)

• Voltage clamp by Kenneth Cole (1900-1984) in 1947

• First giant squid axon potentials
• Start of neurophysiology

The first computer tomograph in 1971 Patch clamp single neuron electric response

Erwin Neher
Sir Godfrey (1944-) and Bert
Hounsfield (1919- Sakmann (1942-)
2004) Nobel Price in
Nobel Price 1979 1991
Geographical information systems The R programming language

Developed 1968 by Roger Tomlinson

In epidemiology GIS maps are used

since 1832 (French Cholera map) and Developed in 1995 by Ross Ihaka and Robert
1854 (Cholera map of London) Gentleman at Bell Labs
 Outlook
Gene editing and genome engineering with Experimental Neurobiological
artificial nucleases evolutionary research engineering (since 2000)

• Neural interfaces
• Brain computer
interfaces
• Neural prostheses
• Neurorobotics
• Tissue regeneration
Emanuelle
Jennifer Doudna • Neural enhancement
Charpentier
(1968-) (1964-)

William Dallinger’s (1839-

Clustered regularly interspaced
1909) incubator (1880)
short palindromic
created high temperature
repeats (CRISPR/Cas9)
adapted protists.

• Bio-hackers: will it be possible to hack Richard Lenski’s (1956-)

living organisms from outside? long term Drosophila
• Editing human embryos breeding experiments
• How close are ‚brave new worlds’? How close is brain reading?
(since 1988)