Das Wunder der Vererbung

DiakoniePublik 3/2001Blueprint of Life

Cell

Nucleus

Chromosom

Gene DNA

Gene-product: Protein

Informationsübertragung bei der zellteilung

Cell division: Transfer of Information!

C in phosphate ester chain

C and N in bases

Base pairs

Sugar phosphatebackbone

Minorgroove

Majorgroove

H

O

P

5‘ 3‘

DNA as carrier of Information

Human ß-Globin, Segment ... TAAGCCAGTG CCAGAAGAGC CAAGGACAGG TACGGCTGTC ATCACTTAGA CCTCACCCTG TGGAGCCACA CCCTAGGGTT GGCCAATCTA CTCCCAGGAG CAGGGAGGGC AGGAGCCAGG GCTGGGCATA AAAGTCAGGG CAGAGCCATC TATTGCTTAC ATTTGCTTCT GACACAACTG TGTTCACTAG CAACCTCAAA CAGACACCAT GGTGCACCTG ACTCCTGAGG AGAAGTCTGC CGTTACTGCC CTGTGGGGCA AGGTGAACGT GGATGAAGTT GGTGGTGAGG CCCTGGGCAG GTTGGTATCA AGGTTACAAG ACAGGTTTAA GGAGACCAAT AGAAACTGGG CATGTGGAGA CAGAGAAGAC TCTTGGGTTT CTGATAGGCA CTGACTCTCT CTGCCTATTG GTCTATTTTC CCACCCTTAG GCTGCTGGTG GTCTACCCTT GGACCCAGAG GTTCTTTGAG TCCTTTGGGG ATCTGTCCAC TCCTGATGCT GTTATGGGCA ACCCTAAGGT GAAGGCTCAT GGCAAGAAAG ...

Human ß-Globin, Exon1, Segment ...GTG CAC CTG ACT CCT GAG GAG Val His Leu Thr Pro Glu Glu

AAG TCT GCC GTT ACT GCC CTG Lys Ser Ala Val Thr Ala Leu

TGG GGC AAG GTG AAC GTG ... Trp Gly Lys Val Asn Val + 126 further AS !

TGA Stop !!!

Genomic Library of Mankind

• 46 Chromosomens 2 * 3,2 Milliarden Buchstaben• 30 000 – 40 000 Genes• ca. 99 % not protein-coding• Man/Chimpanzee 1-2% global text difference

(ca. 120 Mio Letters)• enormous repetitive segements • Retroviral Traces (hundreds of thousands)

Genomic Library of Individual Person

• ca. 2 Mio Differences (SNPs)(between non-related persons)

• ca. 60 000 of them in coding regions• ca. 10 000 genetic defects

(each individual carries about 5)

• every 500 -2000 letters a variation

Evolutionary Traces in the Genome

• 25 % of the human genome are „deserts"

• ca. 50 % are repetitions

• among them ca. 45 % „jumping copies",

(silent since millions of years)

• Museum of viral infections

Genomic Non-sensebut important identification tag!

Person 1 : CA CA CA CA CA CA CA(Father ?) CA CA CA CA

Person 2: CA CA CA CA CA CA CA CA CA CA CA CA CA CA CA(Father ?) CA CA CA

Person 3: CA CA CA CA CA CA CACA (Mother) CA CA CA CA CA CA CA

Person 4: CA CA CA CA CA CA CA CA CA CA CA CA CA CA CA(Father ?) CA CA

Person 5: CA CA CA CA CA CA CA(Child) CA CA

Die ersten Stadien des Menschen

First phases of human life

2 cells 4-cells2. day

8-cells morula compacta3. day

Blastocyst4.-7. day

Early embryo in tubal duct

Preimplantation genetic diagnosis PGDGebärmutter

Ovar

Egg cell

Sperm cells

Impregnation

Development towards blastocyst

Withdrawal of a cell

Diagnosis of chromosomal defector genetic disease

Implantation of „healthy“ embryoInto uterus

„“Defective“ embryos areDiscarded and die

DiakoniePublik 3/2001

Stem cells

Stem cells in bone marrow

Early development of embryo

Sperm cell Egg cell

Pronucleus

Zygote

Morula germ

Blastocyst

Nidation

KryoconservationMultiple fertilization

3. dayTotipotency

Selection (PGD)4.-5. day

Withdrawal of embryonic stem cells

Pluripotency5.-7. day

5.-8.(-14.) Tag„primitive streak“ End of twinning 11. Tag

MultipotencyTissue stem cells„adult“

Organogenesis

Neural duct end of 4th weekBrain 8.-12. week

Dolly the cloned sheep

Withdrawal ofbody cells

Withdrawal of fresh ova

Depletion Withdrawal of nucleus

Merging of synchronized cells

Fusion cell(totipotency)

Embryo

Implkantation intoFoster mother

Cloned sheep(genetic copy of cell donor)

Cell membrane

Zona pellucida

DiakoniePublik 3/2001Reproductive Cloning

Donor personto be cloned Donor of egg cells

Early embryo

Implantation of embryo intoUterus of woman

Foster mother

Cloned child

Nucleus with genetic information

Body cell

Enucleated egg cell

Geklonte Orginale

Germ line engineeringEgg cell

Sperm cell

Fertilization

Embryo with „defective“genome

Withdrawal of cell

Implantation of normal gene

Birth of a baby without The new propertyRepaired egg cell

Becomes embryo

DiakoniePublik 3/2001

Human-Genom-Projekt und seine Auswirkungen

Founding of Principal Human Rights in a Written Constitution

German Basic Law (1949), Article 1 :

Die Würde des Menschen ist unantastbar. Sie zu achten und zu schützen ist Verpflichtung aller staatlichen Gewalt. (The dignity of man is untouchable. The state authority is obliged to respect and to protect it.)

Constitution of the U.S. (1787):

We the people of the United States, in order to form a more perfect union, establish justice, insure domestic tranquility, provide for the common defense, promote the general welfare, and secure the blessings of liberty to ourselves and our posterity, do ordain and establish this Constitution for the United States of America

Declaration of Independence of the U.S. (1776):

We hold these Truths to be self-evident, that all Men are created equal, that they are endowed by their Creator with certain unalienable Rights, that among these are Life, Liberty and the Pursuit of Happiness

Immanuel Kant "Grundlegung zur Metaphysik der Sitten" (1785)

"Groundwork to the Metaphysic of Morals"

"Der kategorische Imperativ ist also nur einziger und zwar dieser:handle nur nach derjenigen Maxime, durch die du zugleich wollen kannst,

daß sie ein allgemeines Gesetz werde".

"Der Mensch und überhaupt jedes vernünftige Wesen existiert als Zweck an sich selbst nicht bloß als Mittel zum beliebigen Gebrauche für diesen oder jenen Willen, sondern muß in allen seinen sowohl auf sich selbst, als auch auf andere vernünftige Wesen gerichtete Handlungen jederzeit zugleich als Zweck betrachtet werden".

not solely a means, but at the same time an end in itself

"Was die Bedingung ausmacht, unter der allein etwas Zweck an sich selbst sein kann, hat nicht bloß einen relativen Wert, d.i. einen Preis, sondern einen inneren Wert, d.i. Würde".

not solely a relative value,i.e. a price, but an inner value, i.e. dignity

Zweck an sich selbst: end in itself

Jeremy Bentham vs. Immanuel Kant

Consequentialist vs. Deontological Ethics

Extreme positions:

Jeremy Bentham (1748-1832): "Principles of Morals and Legislation" 1789• Utility for producing the greatest happiness (least displeasure) of the greatest number• Judgment of practical value, evaluation of options

Immanuel Kant (1724-1804): "Groundwork to a Metaphysic of Morals" 1785• Fulfillment of the autonomous will of a rational (self-conscious) (human) being• Judgment of obligation, statement of categorical duties

(Note: there are theories that found morals outside (or beyond) those principles)

What is a Human Being? (in terms of biology)• Numerous definitions in history. Example: Animation (inspiration) at 40th day of pregnancy

Modern Convention:

• Any living entity with the full potential to become a human being• beginning with the fertilized egg after conjugation of DNS• including totipotent human cell

Alternative Convention:

Human embryo after nidation into the maternal uterus

Attitude Towards Gene Medicine and Artificial Procreation

Pragmatic vs. Fundamental Approach

Utility vs. Categorical Obligation

Jeremy Bentham vs. Immanuel Kant

Law Regulating Import of Embryonic Stem Cells (2002)

•Import forbidden in principle•Qualified exceptions•Only from „superfluous“ embryos•Superfluous due to reasons not concerning the embryo (exclusion of discarded embryos)

•With written informed consent of donors•No material benefits to donors•Only for cell lines established before 2002 (exclusion of „ordered“ stem cells

• Law applies to academic and privately funded research

Risk

Risk = cost of case * probability of event + cost of screening

Total genetic risk

Each person belongs to a few risk groups for a disease with genetic component

Thus in principle everybody should pay a risk surchargeFor all persons this will cancel

Provided that equity of information is eastablished between insuranceand client!