Legal issues related to genetic diagnostics Genomic Information Non-discrimination Act (GINA) what is covered, what not

1. Legal issues related to genetic diagnostics Genomic Information Non-discrimination Act (GINA) what is covered, what not risk alleles for Alzheimers disease long-term care insurance adverse selection Patents - theoretical quid pro quo weighing benefits vs harms BRCA genes and suit challenging their patents

2. GINA, passed 2008 Who can’t discriminate based on genetic information? health insurers, employers What can’t they do - use genetic info as criterion for offering policy, setting rates, offering job Can they even ask for/use genetic information? Possible undesired consequence – can’t offer dis. risk reduction programs (e.g. wt. reduc. for diabetes) to those at greater risk Who can discriminate based on genetic information? life, disability, long-term care (LTC) insurers

3. ApoE genotypes, risk for Alzheimers disease, LTC insurance What is Alzheimers disease (AD)? Is it preventable? effectively treatable? ApoE genotype AD incidence < age 85 genotype freq. not e4/not e4 ~10% ~75% e4/not e4 ~30% ~25% e4/e4 ~80% ~1% Would you like to know your ApoE genotype? What would you do if you learned you carried e4? see NIH symp. on impact of genome seq. 2/10/11 www.videocast.nih.gov for some responses

4. Is nursing home care covered by medicare? medicaid? – under what circumstances? What is long-term care insurance (LTCI)? Is AD the major cause of LTC claims/costs? ~33% of claims, 50% of costs Do people who learn they carry e4 tend to buy LTCI? small study found odds ratio ~5 Is this “adverse selection”?

5. Ethical issue – should you be able to keep your ApoE genotype secret from LTC insurers? arguments for arguments against What are expected effects under diff. scenarios on LTCI rates? see N. Amer. Act. J. 5 (2) 54, 2001 Can your apoE genotype can be inferred from 23andMe SNP test results? Could this affect your ability to get LTCI? Might it affect other things in your life that you haven’t considered? Can you keep this info private? A possible student project?...

6. Patent Theory Economists: patents provide necessary incentives for companies to invest in R&D; but companies could invest in R&D and keep their inventions secret US Constitution (Art. I, section 8): “Congress shall have power .. to promote the progress of science and useful arts, by securing for limited times to authors and inventors the exclusive right to their respective writings and discoveries.” Theory: society gets more benefit by having companies disclose their inventions, in return for limited term of monopoly (basic quid pro quo) Note patents definitely harm consumers in short run by allowing monopoly prices

7. Patent law – invention must be new, “non-obvious”, useful, and fully disclosed Tension in law (Supreme Court decisions) about patent limitations: can’t patent natural laws, products of nature on grounds that this would inhibit progress (violation of intent of Art. I Sec. 8) but human ingenuity sometimes held to trump natural product limitation – e.g. patent on purified adrenalin (Hand decision); and patents on genes (~20% of human genes now said to be patented) does this debate reflect differing views on what promotes vs inhibits industry?

8. Myriad patents – What are BRCA1/2? 2 genes which when mutated -> hereditary breast CA General life-time incidence breast cancer ~8% of women With BRCA mutation, up to 40-80% (10x) onset often at younger age (30s), risk by age 50 up 25x cancer can be bilateral, occur in men also inc. risk of ovarian cancer BRCA proteins are involved in DNA repair why “dominant”? Normal allele sometimes lost by somatic mutation, then mutations not repaired, -> tumor

9. Myriad patents on BRCA genes – for video on controversy watch 60 minutes at http://www.cbsnews.com/video/watch/?id=6362525n&tag=contentMain;contentBody Discovered using US gov’t funds. Is this relevant? Bayh-Dole Act allows individuals, universities to patent fruits of gov’t. sponsored research Was invention new, useful, non-obvious, fully disclosed? Should unspecified mutations in BRCA be covered bec. Myriad found BRCA were cancer genes? Does Myriad provide diagnostic service responsibly? Does it license right to test for BRCA mutations? Is it required to?

10. Can screening prevent breast cancer in women w/ BRCA mutations? Can surgical removal of breasts and ovaries? Estrogen blocking drugs? What fraction of breast cancer is hereditary? ~5% What is BRCA mutation frequency in diff. ethnic groups? ~ 1% in East. Eur. Jews ?~ 0.1% in general population

11. What motivated American Civil Liberties Union (ACLU) challenge in complaint? Social costs some women can’t afford tests; women can’t get “second opinion” confirmation before taking serious action (e.g. surgery) tests could be done more cheaply if no monopoly Are these legal objections, or expected consequences of monopoly?

12. ACLU’s legal objections in memo for Summary Judgment Product claims for BRCA genes are improper as genes are natural products Process claims (e.g. method of testing for cancer susceptibility based on comparing pt’s. BRCA seq. to wild-type seq.) are overly broad, hence hinder science, and effectively inhibit freedom of thought (violate 1st amend.)

13. Other arguments against gene patents – SACGHS report • Large # patent holders of individual genes may inhibit • development of more potent technologies (multiplex • testing for 106 SNPs at once , genome sequencing): • but this kind of issue may be solved by market: • multiplicity of patents on radio components -> • formation of new company of patent holders, RCA • 2. Empirically, patents don’t seem necessary for • commercialization of gene diagnostic tests since • many companies offer them on non-patented • genes (e.g. CF, Tay-Sachs)

14. What could be done if gene patents upheld? SACGHS recommends Congress pass a law to exempt from patent infringement liability those who perform diagnostic gene testing How do you think case should be decided? What did District Court judge decide? Will this be appealed? Get to Supreme Court? What is position of Obama Dept. of Justice?

15. Homework read commentary on GINA watch “60 minutes” video Divide and conquer: read one of the other (non-FYI) items on Blackboard