Gènes, Médicaments, Culture et Santé de l Homme

Transcription

1 Gènes, Médicaments, Culture et Santé de l Homme Miroslav RADMAN Professeur / Directeur Université Paris-V Faculté de Médecine Necker-Enfants Malades, INSERM U571 :

2

3 Robot Scientists: résults

4 Gaussian Distribution of Quantitative Traits (IQ as an example)

5

6 Survival Curves for People 160 vs. 1990

7 Tuberculosis Deaths

8 Record Female Life Expectancy

9 Female Life Expectancy: Years & Countries

10 Both death rate and medical cost grow exponentially with age Death rate French women 94 1,1,01 1E-3 1E age Medical cost France age

11 Medical expenditure & death rate are highly correlated 1 death rate,1,01,001, medical expenditure 80 90

12 Cumulative Cancer Risk: Human & Rat

13 «As long as they are mortals, human beings won't be totally relaxed» Woody Allen

14 HOW GOOD IS OUR GENOME? Phil. Trans. R. Soc. Lond. B (2004) 359: 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?

15 P53 Pathways of Cancer Prevention

16 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) and their first degree relatives with a 50% chance of carrying the mutation Tumors types number of cases % Breast carcinoma ,1% Soft tissue Tumors sarcomatypes number 124 of cases 21,7% % Brain tumor Breast carcinoma ,2% 33,1% Bone sarcoma 89 15,9% Soft tissue sarcoma 124 Adenocortical carcinoma 32 5,6% 21,7% Brain tumor Acute leukemia ,2% 3,5% Bone sarcoma ,9% 100 Adenocortical carcinoma 32 5,6% Acute leukemia 20 3,5% 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 738 cancers were developped identified 224 in 185 cancers patients (30%) and families before with age a 20 P53 and germline 265 cancers mutation (36%). These in patients the third developped and fourth 224 cancers decades. (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

17 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.

18 M. Serrano s lab. & J.-C. Weill Garcia-Cao et al.

19 BAC Constructs for p53 Transgenesis

20 3rd p53 gene copy

21 Extra p53 genes protect mice from cancer

22 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

23

24 Cartoon by Philippe Geluck