1. Mainstreaming Genetic Medicine: A Golden Opportunity for Genetic Counselors National Society for Genetic Counselors November 4, 2001 Francis S. Collins, M.D., Ph.D.

4. Mar 1999 Apr 1999 Mar 1999 Apr 1999 May 1999 Mar 1999 Apr 1999 May 1999 Jun 1999 Mar 1999 Apr 1999 May 1999 Jun 1999 Jul 1999 Mar 1999 Apr 1999 May 1999 Jun 1999 Jul 1999 Aug 1999 Mar 1999 Apr 1999 May 1999 Jun 1999 Jul 1999 Aug 1999 Sep 1999 Oct 1999 Mar 1999 Apr 1999 May 1999 Jun 1999 Jul 1999 Aug 1999 Sep 1999 Oct 1999 Nov 1999 Mar 1999 Apr 1999 May 1999 Jun 1999 Jul 1999 Aug 1999 Sep 1999 Oct 1999 Nov 1999 Dec 1999 Mar 1999 Apr 1999 May 1999 Jun 1999 Jul 1999 Aug 1999 Sep 1999 Oct 1999 Nov 1999 Dec 1999 Jan 2000 Mar 1999 Apr 1999 May 1999 Jun 1999 Jul 1999 Aug 1999 Sep 1999 Oct 1999 Nov 1999 Dec 1999 Jan 2000 Feb 2000 Mar 1999 Apr 1999 May 1999 Jun 1999 Jul 1999 Aug 1999 Sep 1999 Oct 1999 Nov 1999 Dec 1999 Jan 2000 Feb 2000 Mar 2000 Mar 1999 Apr 1999 May 1999 Jun 1999 Jul 1999 Aug 1999 Sep 1999 Oct 1999 Nov 1999 Dec 1999 Jan 2000 Feb 2000 Mar 2000 Apr 2000 Mar 1999 Apr 1999 May 1999 Jun 1999 Jul 1999 Aug 1999 Sep 1999 Oct 1999 Nov 1999 Dec 1999 Jan 2000 Feb 2000 Mar 2000 Apr 2000 May 2000 Human Genome Sequencing

7. A SAMPLING OF COOL THINGS ABOUT THE GENOME Humans have fewer genes than expected Human genes make more proteins than those of other critters Male mutation rate is twice that of females “Junk” DNA contains the remnants and raw materials for evolution

8. Comparative Genomics Proteomics Functional Genomics Fulfilling the Promise of Genomics for Better Health Medical Genomics

10. Positional cloning of a gene for a highly penetrant Mendelian disorder is now straightforward – but tracking genetic susceptibility factors for non-Mendelian disorders continues to be vexing

11. Association is much more powerful than linkage to identify common susceptibility variants Risch and Merikangas, Science 273: 1516-1517, 1996

12. But until now, association studies have only been practical when a candidate gene was suspected -- and usually we’re not smart enough to pick the right candidates

16. Haplotypes from 258 chromosomes on 5q31 Daly et al., Nature Genetics Oct. 2001

17. ~ 60 kb

18. SIMMap: A New Map of Human Shared Inheritance for Medicine Goal is to define all common haplotypes Genome-wide association studies can then be done with a “gold standard” set of SNPs that define common alleles Pilot studies underway to determine how many populations to sample, and best strategy for defining haplotype blocks

22. Experience in CF carrier screening at Kaiser Permanente (Witt and Coppinger, ASHG) Screened 27,000 women in a large HMO for 37 CFTR mutations 1/28 found to be a CF carrier Only 10% of carriers wanted face-to-face counseling 63% were ) F508, 12% R117H Complexities: counseling for mild mutations, 5T/7T/9T in intron 9, asymptomatic women with two CF mutations,…..

24. Gleevec™ – Specifically Targets An Abnormal Protein, Blocking Its Ability To Cause Chronic Myeloid Leukemia Chromosome 9;22 translocation CML Bcr-Abl fusion protein Gleevec™ Bcr-Abl fusion protein Normal

26. Who will practice genomic medicine?

28. Arguments against mainstreaming of clinical genetic services: Most primary care providers (PCPs) lack training in genetics, and display little interest in learning these skills PCPs are likely to be more directive PCPs may focus on individual, ignore family Managed care places tight time constraints on PCP visits Medical geneticists and genetic counselors will be negatively affected

29. Arguments in favor of mainstreaming of clinical genetic services: Demand for services will exceed capability of specialists Integrates genetic services with comprehensive holistic longitudinal medical management Incorporates genetic information into pre-existing models of health behavior modification Provides a better opportunity for provision of genetic services to diverse segments of society

30. Prior examples where specialty fields have been positively affected by mainstreaming the basic discipline Infectious disease Nutrition Human development Diabetes care Seizure management

32. New and interesting roles for genetic counselors: Training primary care providers in provision of basic genetic services Developing new models for providing services and conveying risk information Establishing referral networks for primary care providers Coordinating research studies that connect genotypes with phenotypes Advising biotechnology, diagnostic, and pharmaceutical companies Providing advice to government – FDA, NIH, HRSA, CMMS, Congress

33. National Coalition for Health Professional Education in Genetics (NCHPEG) Executive Director: Joe McInerney www.nchpeg.org

34. Difficult problems: Developing more cost-effective ways of delivering quality genetic services – is our time-intensive model a luxury that cannot be sustained? Achieving adequate reimbursement – will involvement of PCPs increase or decrease the overall likelihood of financial compensation for genetic services?

36. 2010 -- Predictive genetic tests available for a dozen conditions -- Interventions to reduce risk available for several of these -- Will reasonably effective legislative solutions to genetic discrimination be in place? BUT…. Mainstreaming of individualized preventive medicine -- Who will deliver services? How will they be reimbursed? Will access be inequitable? -- Pharmacogenomics is standard of care for several drugs

37. 2020 -- Gene-based designer drugs available for diabetes, Alzheimer’s… -- Gene therapy standard of care for several conditions -- Major anti-technology movements active in US, elsewhere BUT…. Genomic therapeutic revolution in full swing -- Intense debate underway on non-medical uses of genetics -- Sequencing a complete human genome costs $5,000 or less

38. 2030 -- Preventive and therapeutic strategies available for most diseases -- Illnesses detected early by molecular surveillance BUT…. Genomics-based health care is the norm -- Social Security goes under as average life expectancy reaches 90