information

Vorlesung Forschungsethik der biomedizinischen
Wissenschaften
Master MLS/MIW, 2. Semester, SS 2012
Genetik und Genomik
3. Juli 2012
Christoph Rehmann-Sutter
Prof. für Theorie und Ethik der Biowissenschaften
[email protected]
www.imgwf.uni-luebeck.de
These:
Das Genom hat im Verlauf seiner Entzifferung seine
Identität gewechselt
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Es ist immer noch dasselbe Molekül (DNA) geblieben, aber es
bedeutet für uns nicht mehr dasselbe.
Wechsel vom genetischen Programm zur System-Genomik
Einflussfaktoren (u.a.):
– Verständnis einzelner Gene und ihrer Funktionen in der
Entwicklung des Phänotyps auf molekularem Niveau
– Multiple, kontextabhängige Funktionen von DNASequenzabschnitten, Systembiologie
– Forschung mit großen Datenmengen (-omics) und genomweite
Assoziationsstudien
– Theoretische Widersprüche im Programm-Modell des Genoms.
Î Was bedeutet das philosophisch? Gibt es ethische
Implikationen?
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Interpretation
Es kommt drauf an,
was DNA ist!
Berkeley: Lawrence Hall of Science. DNA model/climbing structure (Photo: CRS 1998, 2010)
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Bill Clinton on June 26, 2000 (CNN.com.transcripts)
„Today's announcement represents more than just an effort making
triumph of science and reason. After all, when Galileo
discovered he could use the tools of mathematics and
mechanics to understand the motion of celestial bodies, he felt,
in the words of one imminent researcher, that he had learned
the language in which God recreated the universe. Today we
are learning the language in which God created life.“
www.TheDNAStore.co
Visited: May 14, 2008
Frequently used metaphors to explain genomics
Instruction book
Skript
Bauplan
Information
Architekturplan
Blueprint
“Program”
Code
Book of life
Map
Text
Language
Each metaphor is a messenger of meaning between discourses
(Maasen/Weingart 1995): genetics and anthropology (Menschenbild/
Weltanschauung).
Each metaphor contains a little story to explain the relation between DNA
and the organism and ourselves.
RISC =
RNAinduced
silencing
complex
D. O. Perkins et al. Molecular Psychiatry (2005) 10, 69–78;
www.epialliance.org.au/contents/AboutUs/WhatIsEpigenetics.sht
Widersprüche in der Idee vom “Bauplan” oder
“genetischen Programm”
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Epigenetik
ncRNA
Alternatives Spleissen
Überlappende Gene
Alternative Leseraster
Trans-splicing
Anti-sense transcripts
mRNA editing
Selektive Methylierung der DNA Nucleotide (epigenetisches
Programmieren/Regulieren des Genoms)
Multiple, ‘Orts’-spezifische Funktionen von Genprodukten
…
Gene sind multifunktionell; ihre Wirkung und Funktion hängt vom Kontext ab.
Î Die Molecularbiologie denkt heute nicht mehr in Begriffen des Bauplans und
des genetischen Programms, sondern betrachtet die Zelle als interaktives
System.
The basic picture in systems biology
„Thus the situation is one of mutual influence, not unidirectional
causation. Hence, although the genes can be thought of as in
some sense controlling such processes, in fact it is not true that
an understanding of the genes alone is sufficient for their
complete description. For example, even if we were somehow
able to obtain the DNA of a dinosaur, unless we also knew the
initial conditions of the cellular composition that allow their
proper expression of genes, we would not be able to create a
Jurassic Park. The conclusion we reach from these
considerations is that ... we should be studying models of
interactive dynamics. Then, we should inquire whether, within
such dynamics, the asymmetric relation between two molecules
is generated so that one plays a more controlling role and
therefore can be regarded as the bearer of genetic information.“
Kunihiko Kaneko, Life: An Introduction to Complex Systems
Biology (Berlin: Springer 2006, 20):
Science 2011;331:
„...das definierende Prinzip der Systemgenetik ist,
dass sie verstehen will, wie genetische Information
integriert, koordiniert und dann durch molekulare,
zelluläre und physiologische Netwerke übertragen
wird, um die Funktionen höherer Ordnung und die
emergenten Eigenschaften biologischer Systeme zu
ermöglichen.“
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Assumptions of “program” genomics
1.
DNA (information) has an ontological privilege. DNA has the
status of an organizer molecule, a primary active substance.
Other things are means, requirements or necessary
conditions.
2.
Genetic information is the nucleotide sequence of the
genome.
3.
Structures and capabilities are results of the execution of a
kind of instructions, which are present in the sequences of
DNA.
4.
Hereditary bottleneck assumption.
Assumptions of “system” genomics
1.
2.
3.
4.
DNA (information) has no ontological privilege. DNA is an
organ of the organism like all other components and
processes of cells. It differs only by the special character of its
interactions.
Genetic information is the information that is actually pertinent
for developmental steps. It is continually produced during
development, in the course of the interactions between DNA,
cells and environment. Genetic information has itself an
ontogeny, is temporally and locally present.
Structures and capabilities are not only results of informed
developmental steps but appear also as causes for further
developmental steps.
No hereditary bottleneck; no genetic reductionism.
Ta b . 1: T wo c on t rasti ng v ie w s o f g ene s and t h e g en om e -o r g an is m
relat io n sh ip.
program the ory o f DN A
syst em ic t h e o r y o f
DNA
Reg ul ar ity is
ex pl ai n e d as t h e …
real izati on o f g ene t ic
inf o rm ati on/ imp le m e n tati
o n of pr e d eter mi ne d sets
o f inst ru ct io ns .
”h ist or ic al” su c c essi on
o f c o mp lex
c on ste llat io n s o f
c ause s.
( ii)
Cau sal o r d e r:
DNA n ee d s o t h er f act o rs
f or it s ad e qu ate
ex pr essi on .
A ll f act or s are
n eces sar y ; DNA is n o t
pr iv il ege d as sup er io r
c ause .
( iii)
Gen eti c inf o rm ati on
…
pr eexists
is ge n e r ate d in
d e v el opm ent al
in te r ac t io n s.
( iv)
Mic ro st ru c t u re , t h e
”p la c e ” o f DNA in te rac t io n s …
is su bo r di nat ed , as o n e
o f t h e n eces sar y
c ond it io n s f or g ene
ex pr essi on .
m atte rs p e r se , as o n e
d ist in ct k ind o f c ause
in d e v el opm e n tal
syst ems .
(v)
En v ir onm e n tal
inf lu e n ces are
d es c r ibe d b y a …
n o rm o f
react io n/ph e n ot y p ic
p la stic ity .
c or r elat o r y f un ct io n .
( i)
d e v el opm ent .
Presymptomatic genetic tests
Program genomics:
System genomics:
A mutation in a cancer-related
gene is understood as
information for making
cancer.
A mutation in a cancer-related
gene is an indicator for an
elevated likelihood that the
body and its circumstances
could together produce the
information that leads to
cancer.
The mutation does not indicate
information for making
cancer.
Understanding the embodied self
Program genomics:
System genomics:
The body is essentially a
product of its genetic
sequences.
Embodiment (development) is
an act of executing
instructions imposed by the
inherited genetic information
(the invisible genotype).
Organisms are survival
machines of their genes.
The body is seen as the author
of its genetic information.
Embodiment is a self-informing
developmental process,
which retrospectively can be
explained as following a
pattern.
Developing, organisms
integrate their dynamic
features into a new moment
of presence.
Understanding the practices that need to be
regulated
1) A testable mutation in a disease-related gene is an indicator
for an elevated likelihood that the body and its circumstances
could together produce the information that leads to the disease
(“risk factor”). The mutated allele is not the ‘information for the
disease’, or an ‘instruction for developing the disease
symptoms’.
2) A whole individual genome sequence is a personalized
conundrum, containing a set of answers to known questions
and another set of potential answers to yet unknown questions:
a developing informational resource with implications for the
individual. To have one‘s genome sequence makes both sets of
answers accessible to all parties who have access to the
sequence. The sequence is a peremptory total gene test whose
content continually changes.
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Ziel einer guten Regelung
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Ziel der Politik; ein gutes Leben und die Freiheit der BürgerInnen
ermöglichen;
Dies schließt ein: Gesundheit, Handlungsfähigkeit, Beziehungen,
Privatsphäre, etc.;
Erfahrungen aus der PND: Grenzen der Nichtdirektivität
(„Autonomieansatz“);
In einem sich so rasch entwickelnden Handlungsbereich ist eine
begleitende Erforschung der ethischen, rechtlichen und sozialen
Implikationen (ELSI) Voraussetzung für das Gelingen einer guten
Regelung (‚good governance‘);
Automatismen (technologischer Imperativ, Systemzwänge) können
Freiheit und gutes Leben in Frage stellen.
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Offene Fragen im Bezug auf genetische Information
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Wofür ist die genetische Information Symbol (biologische v.
psychische Ebene)?
• Bedeutung für wen (Eltern, Kind, Ärztin/Arzt)?
• Jetzt und später (Erzählung, Erinnerungen,
Lebensgeschichte)?
• Sind Geheimnisse, Nichtwissen im Bezug auf Zukunft immer
schlecht?
• Multigentests (Chips), whole genome scans (exome
sequencing)?
• Handlungsfähigkeit ≠ (>) informed consent.
• Kindeswohl: Wie verändern sich unsere Vorstellungen von
einer „guten Kindheit“ als Teil eines „guten Lebens“? Wie
verändern sich die elterlichen Pflichten?
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Paradox der Prädiktion:
Bei der Maximierung des Wissens um die Zukunft droht genau
das verlorenzugehen, in das man gerne blicken möchte:
die Zukunft. Zukunft als eigentliches Noch-Nicht kann nur
ein unendlich offener Möglichkeitsraum sein.
Die Kolonialisierung der Zukunft durch gegenwärtige
Wissensansprüche vernichtet möglicherweise diese selbst.
Auch die Genetik blickt nicht wirklich in die Zukunft (wie auch
ein Tarot oder ein Horoskop nicht).
The child‘s right to an open future (Joel Feinberg)
v. the parental investment factor (Dena Davis)
Literatur
Dena Davis: Genetic Dilemmas. Reproductive Technology, Parental
Choices, and Children‘s Futures. New York: Routledge 2001.
Eva M. Neumann-Held / Christoph Rehmann-Sutter (eds.): Genes in
Development. Re-Reading the Molecular Paradigm. Durham: Duke UP
2006
Christoph Rehmann-Sutter / Hansjakob Müller (eds.): Disclosure
Dilemmas. Ethics of Genetic Prognosis after the ‚Right to Know/Not to
Know‘ Debate. Farnham: Ashgate 2009.
Christoph Rehmann-Sutter: Zwischen den Molekülen. Beiträge zur
Philosophie der Genetik. Tübingen: Francke 2005.