Transcript 19.1300.David

Bioethics Concerns in Regulating
Large DNA Collections:
The Israeli Experience
David Gurwitz
National Laboratory for the Genetics of Israeli Populations
Sackler Faculty of Medicine, Tel-Aviv University
[email protected]
ABC, Bangkok, Thailand, March 19, 2007
http://nlgip.tau.ac.il
Israelis Are Ethnically Diverse
Jews immigrated to Israel from Asian, African and
European countries, from communities that were
genetically isolated for 1000 – 2000 years
Israeli Arabs include groups with minimal admixture:
Palestinians, Bedouine, Druze
This ethnic diversity is important in clinicla genetics
and pharmacogenetics research
Jewish immigration to Israel: 1948 - 2005
(thousands of immigrants)
26
854 (mostly recent)
2 18 171
24
38
30
273
4 10 43
2
345
24
36
8
61
10
130
76
37
52
59
28
The National Laboratory for the
Genetics of Israeli Populations
• The repository includes about 2000 cell lines and
matching DNA samples, representing the ethnic
diversity of the populations of Israel
• Blood samples for preparation of cell lines
are obtained from adult individuals (>18 y)
with informed consent
• Supervised by the TAU IRB
http://nlgip.tau.ac.il
Cell Lines in the NLGIP Collection
Ashkenazi Jews
Arab
Arabs
Arabs
18%
29%
Sephardic
7%
Ethiopian
Jews
3%
16%
27%
Oriental Jews
North-African Jews
Major Public Collections of Human
Cell Lines and DNA samples
Repository Human Lines Disease
Ethnicity
•
•
•
•
few
Coriell:
~8,000
genetic
ATCC: ~1,500 cancer
ECACC:
~25,000 genetic
Genethon:
~43,000 genetic
• NLGIP:
~2,000
healthy
few
few
few
all
Coding the samples
• DNA samples are coded by four-digit codes
• The only information supplied : ethnicity and gender
• Example for information accompanying a DNA shipment:
Unrelated Ashkenazi donors:
Males
1102 1106 1113 1116 1154 1162 1254 1267 1363 1369
Females
1121 1124 1128 1129 1131 1133 1163 1265 1282 1283
From the NLGIP DNA Request Form:
I, the undersigned, state that:
- The requested cell lines/DNA samples will be used
in my laboratory only for research.
- The cell lines/DNA samples will not be further
distributed to other laboratories or any scientists.
DNA Samples distributed by NLGIP:
By Ethnic Groups
Arabs
15%
Ashkenazi Jews
44%
Ethiopian
4%
Oriental
14%
North-African Jews
16%
Sephardic Jews
7%
DNA Samples distributed by NLGIP:
By Countries
UK
7%
Canada
5%
Italy Others
1%
3%
Japan
14%
USA
43%
Israel
27%
DNA Samples distributed by NLGIP:
By Type of Institute
Other Research Centers 6%
National Research Institutes
28%
Universities
66%
Acetaminophen can be toxic!
Glucuronidation (60%)
HN
HN
COCH 3
HN
UGT
O
Sulfation (35%)
COCH 3
O
CO 2 H
OH
HO
OH
COCH 3
GST
OH
CYP2E1(5%)
N
COCH 3
Toxic!
O
O
SO 3 H
Ethnic Diversity Studies are
Essential for Drug Development
• Polymorphic allele distribution differs between ethnic groups –
- therefore Drug Safety and Efficacy also differs.
• A KEY PROBLEM:
Most clinical trials are performed in Caucasians
• Asians and Africans do not always enjoy the
same level of safety and efficacy from new medicines
Heart failure in Caucasians vs. African-Americans
Exner et al. (2001) NEJM 344, 1351-1357
*Enalapril (ACE inhibitor)  No advantage for African-Americans
CYP2D6 & CYP2C19
Luo et al (2004) American Journal of Pharmacogenomics 4: 395-401
Middle Eastern Origin of the Jews
Hammer et al. (2000) Proc Natl Acad Sci U S A 97, 6769-6774
NLGIP Informed Consent Form
• The blood sample shall be used for preparing
a cell line for research and is not related to
my medical care.
• The repository must maintain the confidentiality of the
information resulting from the research, and use it
without any identifying details.
Informed Consent Form (cont.)
- Altruism is empahsized
• My refusal to participate in this research will not affect
my medical treatment in any way.
• The individual information from such studies shall not
be made available to me.
• I shall not receive any benefit in return for giving my
blood sample and this consent.
Refusal do donate to NLGIP:
Women and >50 are more likely to donate
By Gender
By Age
18-30
37%
31-40 41-50 51-60 Over 60
41% 39% 20%
25%
%
Women
28%
Men
43%
Total
34%
%
%
%
%
%
%
%
%
%
%
%
Reasons for refusal do donate
(asked to choose from 5 optional replies)
60%  Not willing to donate too much blood
24%  Worried that their identity will be exposed
8%  Do not want their genes to be studied
4%  Find it immoral to perform genetic studies
4%  Other reasons
Personalized Medicine:
Can it co-exist with healthcare equity?
• What should we do about people who do not have
the ‘right genotype’ for available medicines?
• How can society ensure better equity in healthcare,
along with better, more personalized, medicine?
***
Questions?
[email protected]