Bioethics Concerns in Regulating Large DNA Collections:The Israeli Experience

David GurwitzNational Laboratory for the Genetics of Israeli Populations

Sackler Faculty of Medicine, Tel-Aviv Universitygurwitz@post.tau.ac.il

ABC, Bangkok, Thailand, March 19, 2007

http://nlgip.tau.ac.il

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

Israelis Are Ethnically Diverse

Jewish immigration to Israel: 1948 - 2005(thousands of immigrants)

854 (mostly recent)

345

273

171

130 76

61

52

59

43

3736

38 30

28

2624

18

10

10

84

24

2

2

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

18%

7%

16%

27%

3%

29%

ArabsArabArabsAshkenazi Jews

Sephardic

North-African Jews

Oriental Jews

Ethiopian Jews

Major Public Collections of Human Cell Lines and DNA samples

Repository Human Lines Disease Ethnicity

• Coriell: ~8,000 genetic few

• ATCC: ~1,500 cancer few

• ECACC: ~25,000 genetic few

• Genethon: ~43,000 genetic few

• NLGIP: ~2,000 healthy 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:

Males1102 1106 1113 1116 1154 1162 1254 1267 1363 1369Females1121 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

Ashkenazi Jews44%

Arabs 15%

Sephardic Jews7%

North-African Jews16%

Oriental14%

Ethiopian4%

DNA Samples distributed by NLGIP:By Countries

USA43%

Israel27%

Japan14%

UK7%

Canada5%

Italy3%

Others1%

DNA Samples distributed by NLGIP:By Type of Institute

Universities66%

National Research Institutes28%

Other Research Centers 6%

HN

COCH 3

OH

HN

COCH 3

OSO 3H

HN

COCH 3

OO CO 2H

OH

OHHO

Acetaminophen can be toxic!

Sulfation (35%)Glucuronidation (60%) N

O

COCH 3

CYP2E1(5%)

Toxic!

UGT GST

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 thesame 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 JewsHammer 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

0%

10%

20%

30%

40%

50%

123

By GenderTotal34%

Men43%

Women28%

By Age

0%

10%

20%

30%

40%

50%

12345

18-3037%

31-4041%

41-5039%

51-6020%

Over 6025%

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?

gurwitz@post.tau.ac.il