Gènes, Médicaments, Culture et Santé de l’Homme Miroslav RADMAN Professeur / Directeur

Gènes, Médicaments, Culture
et Santé de l’Homme
Miroslav RADMAN
Professeur / Directeur
Université Paris-V
Faculté de Médecine Necker-Enfants Malades,
INSERM U571
Genopole® :
Genopole®
La médecine de demain s’invente aujourd’hui
La médecine de demain s’invente aujourd’hui
Genopole®
La médecine de demain s’invente aujourd’hui
Robot Scientists: résults
Genopole®
La médecine de demain s’invente aujourd’hui
Gaussian Distribution of Quantitative Traits (IQ as an example)
Genopole®
La médecine de demain s’invente aujourd’hui
Genopole®
La médecine de demain s’invente aujourd’hui
Survival Curves for People 160 vs. 1990
Genopole®
La médecine de demain s’invente aujourd’hui
Tuberculosis Deaths 1840-1970
Genopole®
La médecine de demain s’invente aujourd’hui
Record Female Life Expectancy
Genopole®
La médecine de demain s’invente aujourd’hui
Female Life Expectancy: Years & Countries
Genopole®
La médecine de demain s’invente aujourd’hui
Both death rate and medical cost grow exponentially with age
1000
Medical cost France
Death rate French women ‘94
1
,1
,01
1E-3
1E-4
100
10
0
20
40
age
60
80
100
0
10
20
30
40
50
60
70
80
90
100
age
Genopole®
La médecine de demain s’invente aujourd’hui
Medical expenditure & death rate are highly correlated
1
90
death rate
,1
80
,01
1
70
60
50
40
,001
30
20
10
,0001
10
100
1000
medical expenditure
Genopole®
La médecine de demain s’invente aujourd’hui
Cumulative Cancer Risk: Human & Rat
Genopole®
La médecine de demain s’invente aujourd’hui
« As long as they are
mortals, human beings
won't be totally relaxed
»
Woody Allen
Genopole®
La médecine de demain s’invente aujourd’hui
HOW GOOD IS OUR
GENOME?
•
Phil. Trans. R. Soc. Lond. B (2004) 359: 95-98
Jean-Claude Weill & M. Radman
P
The answer: Very good for itself (germ line); not so good
for us (soma). We shall see that it could easily do a lot
more for us - make us live longer and better - but has no
interest in post-reproductive soma !
The possessive is wrong: it ’s not “our” genes, it ’s “genes’
us”! Genes use us for their own reproduction, then dispose of
us, abandon us. If we are there only for the benefit of “our”
selfish genes, why not start thinking of outsmarting them by
modifying the germ line for the benefit of the selfish soma?
Genopole®
La médecine de demain s’invente aujourd’hui
P53 Pathways of Cancer Prevention
Genopole®
La médecine de demain s’invente aujourd’hui
Tumor spectrum in carriers of an heterozygous germline P53 mutation :
(Li-Fraumeni syndrome)
Tumor spectrum in carriers
of an heterozygous germline P53 mutation :
and their first degree relatives with a 50% chance of carrying the mutation
(Li- Fraumeni syndrome)
Tumors types
and their first degree relatives with a 50% chance of carrying the mutation
number of cases
Breast carcinoma
189
Soft tissueTumors
sarcoma types
115
Bone sarcoma
89
Adenocortical carcinoma
32
Soft tissue sarcoma
Brain tumor
Acute leukemia
Bone sarcoma
33,1%
124of cases
number
Brain tumor
Breast carcinoma
%
189
124
21,7%
%
20,2%
15,9%
5,6%
115
33,1%
21,7%
20
20,2%
3,5%
89
569
15,9%
100
Adenocortical carcinoma
32
5,6%
Acute leukemia
20
3,5%
569
100
+169 tumors less frequently associated with Li- Fraumeni (stomach, ovary, colon, anal rectum)
+169 tumors less frequently associated with Li-Fraumeni (stomach, ovary, colon, anal rectum)
738 cancers were identified in 185 patients and families with a P53 germline mutation . These patients
developped
cancers
(30%)
beforewith
agea20
265 cancers
the third
and fourth
decades.
738 cancers were
identified224
in 185
patients
and families
P53and
germline
mutation(36%)
. Theseinpatients
developped
224 cancers
(30%) before
age 20 and 265 cancers (36%) in the third and fourth decades.
Data taken from(6)
Data taken from(6)
Table 1
Table 1
Genopole®
La médecine de demain s’invente aujourd’hui
SUMMARY
Cancer incidence versus the number of active p53 genes
(1) No active p53 genes is catastrophic (p53-/- mice).
(2) One p53 gene is better but still too many cancers too early.
(3) Two p53 genes (normal mice and humans): could be better.
(4) Three or four p53 genes (mice): cancer is much reduced
and the life quality and ageing appears normal.
Genopole®
La médecine de demain s’invente aujourd’hui
M. Serrano’s lab. & J.-C. Weill
Garcia-Cao et al.
Genopole®
La médecine de demain s’invente aujourd’hui
BAC Constructs for p53 Transgenesis
Genopole®
La médecine de demain s’invente aujourd’hui
3rd p53 gene copy
Genopole®
La médecine de demain s’invente aujourd’hui
Extra p53 genes protect mice from cancer
Genopole®
La médecine de demain s’invente aujourd’hui
“We humans are the only species
endowed with the capacity to
rebel against the tyranny of our
selfish genes ”
Richard Dawkins
“The Selfish Gene ” 1976
Genopole®
La médecine de demain s’invente aujourd’hui
Genopole®
La médecine de demain s’invente aujourd’hui
Cartoon by Philippe Geluck
Genopole®
La médecine de demain s’invente aujourd’hui