Zosia Bornik & Hadi Dowlatabadi University of British Columbia with thanks to:

1. Explorations in regime change: b-Thalassaemia and the interplay of technological change & social norms. Zosia Bornik & Hadi Dowlatabadi University of British Columbia with thanks to: Sue Cox, Peter Danielson, Ed Levy and Bernadette Modell

2. Overview • Objective of this research • Definitional issues. • Domain information. • Findings. • Conclusions/more 2: Regime Change 14/01/04

3. Objective • At UBC: • Study democratic issues related to applied genomics. • At CMU: • To explore features of regime change. • Synthesis: • What might drive shifts in social norms? 3: Regime Change 14/01/04

4. Social Norms • As a noun: • It describes how a peer group shares specific values and hence chooses among a set of options. • As a verb: • It is used as an approach to risk communication and intervention. It has been successfully employed to address excessive drinking among college students… • Recent History: • Based on research by Alan Berkowitz and H. Wesley Perkins working at Hobart and William Smith Colleges. 4: Regime Change 14/01/04

5. A two-level model of behaviour • Norm based heuristics: • “There are the values we hold” • Deliberated decision: • “I know what is valued and estimate the benefits of this to outweigh its costs …” 5: Regime Change 14/01/04

6. The question: • What makes the higher level of decision-making be revised? • Changing circumstance: • Social • Economic • Technologic • … 6: Regime Change 14/01/04

7. An example:Thalassaemia • Thalassaemia, is an inherited condition where the genes controlling haemoglobin production are affected. • Each hemoglobin molecule contains four subunit proteins (2xa and 2xb). • Hemoglobin properly binds and releases oxygen only when two alpha subunits are connected to two beta subunits. • A pair of genes located on chromosome #16 controls the production of the alpha subunits of hemoglobin. • A single gene located on chromosome #11 controls the production of the hemoglobin beta subunit. 7: Regime Change 14/01/04

8. Its in the genes b-globin genes a-globin genes a2 a1 b1 b2 a3 a4 Hemoglobin Protein Chromosome 16 Chromosome 11 8: Regime Change 14/01/04

9. b-Thalassaemia • When the b-globulin genes (or their neighbours) are defective or absent, the patient suffers from b-Thalassaemia of different severities. • Minor: where haemoglobin production is slightly affected • Intermedia: … • Major: where both genes are affected leading to severe anaemia. • Patients with b-Thalassaemia major need: • chronic blood transfusions • AND • Chelation therapy (to address iron over-load) 9: Regime Change 14/01/04

10. Clinical intervention • Diagnose anaemia • Test for b-trait using haemoglobin electrophoresis • Blood transfusions • Iron-Chelation therapy • ≥2 units of blood/mo. • Liver, heart & other medical problems • ≥15 days/mo. of Chelation therapy • Life expectancy: ~ 60yrs • Cost: CDN$1-2 M 10: Regime Change 14/01/04 Source: Zeuner et al, 1999

11. Social intervention • Identify potential carriers • Give them genetic counselling • Bring pressure to avoid pregnancy • Revised norms on procreation • Cost: CDN$ 6-100/cap 11: Regime Change 14/01/04 Source: Zeuner et al, 1999

12. Test the genes: Pre-natal Give genetic counselling Offer termination of pregnancy Revised norms on abortion Cost: CDN$ 150-1000/test Test the genes: Pre-implantation Give genetic counselling Try in-vitro fertilization again Revised norms on eugenics Cost: CDN$ 4000-5000/test Genomic interventions 12: Regime Change 14/01/04 Sources: Verma 2003, Karczeksi 2003

13. The Thalassaemia Belt • 2-18% of the population consists of carriers (WHO, 1994) • includes Mediterranean Region, Middle East, Indian Subcontinent, and Far East • Population movements have led to dissemination of the gene… • ß-Thalnow widespread in Europe, Americas and Australia. In 2002: • ~ 240 million healthy carriers worldwide. • ~ 200,000 ß-Thalmajor births per year (Cao et al, 2002). 13: Regime Change 14/01/04

14. Fall in Thalassaemia Major with screening Source: Modell 14: Regime Change 14/01/04

15. The choices made in Cyprus • 4% chose a different marriage partner. • 20% chose a smaller final family size. • 76% had selective abortion. Source: Modell 15: Regime Change 14/01/04

16. Fall in Thalassaemia Major Births Source: Modell 16: Regime Change 14/01/04

17. Uptake of pre-natal diagnosis by ethnic group (UK) Source: Modell 17: Regime Change 14/01/04

18. Technological Change Diagnosis Transfusion services Desferri-oxamine Genetic screening Improve infants survival Improve child survival Control health spending Social Change Revise social norms High infant mortality Some get blood transfusions Some get Iron Chelation therapy Most are not born Typically 150/1000 IM drops to ~ 40/1000 of which 17% are ß-Thal major! IM drops by another ~7/1000 18: Regime Change 14/01/04

19. Cyprus: Genetically homogeneous population 2-3 mutations. High prevalence rate 14% carrier rate. Broad public engagement through church, schools and community. Elsewhere: Genetically heterogeneous (e.g., >23 mutations in Iran). Lower prevalence rate (and priority). Dominated by other concerns/norms. Why was Cyprus so successful? 19: Regime Change 14/01/04

20. Conclusions • When pressure is sufficiently high norms can shift (i.e., Cyprus, Italy, Iran). • Perhaps such shifts are more readily accepted because they also address other objectives. • Pressure to “preserve norms” (itself a norm at a higher level) trumps where population is heterogeneous(i.e., UK). 20: Regime Change 14/01/04

21. Clinical Intervention costs from Zeuner et al, 1999 Average life expectancy = 63 years Total lifetime treatment costs for B-thal major = 490,000 British pounds = 123,000 at a 6% discount rate (includes diagnosis, blood transfusion, outpatient visits, costs assoc w/ complications) For costs incurred over different life stages, see Table 33, p.68 Social Intervention costs from Zeuner et al, 1999 Total antenatal screening programme costs per 10,000 population group = 33,869 – 800,060 British pounds (see CB analysis and Table 55, p. 90) (includes carrier screening, counseling, pre-natal Diagnosis, and abortion) Genomic Intervention costs Cost for Pre-natal Diagnosis depends on country India = 150$ Canadian per case (Verma, 2003) USA = 1000$ Canadian per case (Karczeksi, 2003) Predicted costs for Pre-implantation Genetic Diagnosis USA = at least 4000-5000$ Canadian per case (Karczeksi, 2003) 21: Regime Change 14/01/04