Recap of week 1 – Framework ethical theories Utilitarianism – greatest good for greatest #

1. Recap of week 1 – Framework ethical theories Utilitarianism – greatest good for greatest # acts should be judged by their consequences problems – no protections for minority, “utility” may not always be appropriate measure some acts seem wrong despite consequences (pushing innocent guy into the trolley) Kant – humans deserve ultimate respect because they are capable of moral decisions, never “use” them Rawls – fair rules are those you’d accept before knowing your position in society (“veil of ignorance”) Libertarianism – highest value on individual freedom and market solutions; but markets not always fair “Communitarianism” – ok for soc. to require contributions such as taxation for common welfare

2. Ethics is interesting in that we all have sense of justice, right; we can try to figure out why we feel the way we do by confronting other views You may not feel any answer is compelling, but your conscience may not let you opt out, either Class 2 – Medical costs are skyrocketing and this is an ethical-legal-social issue Advances in medical technology – e.g. angio- graphy, stents, pacemakers, dialysis, joint replacements, new types of drugs – is main cause

3. Some questions about CBO report on technology as main cause of skyrocketing medical costs What is CBO? Do they have a bias? How do they conclude technology is main cause? Do you find this argument convincing? How much do they estimate defensive medicine is to blame (table 2)? How much is due to epidemic obesity? Does falling fraction of total costs paid “out of pocket” provide an incentive to consume more?

4. How do they view the relative importance of “one-time” savings (e.g. eliminating waste) vs. slowing the rate of growth? How could information about cost-effectiveness of new technology be used to slow growth rate? Can CMS (Centers for Medicare and Medicaid Services) deny coverage based on cost, if FDA approves a device/therapy? Does FDA take cost into consid.? How do you fell about this? What ethical theories, economic interests are relevant?

5. Recent proposal – CMS require cost-effectiveness data from mfr’s within 3 yrs (why delay?); if evidence insufficient, they reimburse only for cost of older therapy http://160.109.101.132/icrhps/resprog/cevr/newsletter/October%20a.pdf; http://www.hhs.gov/recovery/programs/os/cerbios.html ; http://www.thefiscaltimes.com/Issues/Health-Care/2010/10/05/Health-Care-Reform-CMS-Wants-Proof-to-Pay.aspx http://content.healthaffairs.org/content/25/5/1231.full Is this a clever compromise c/w current law? This is example of issue (and proposed solution) that could make a great student term paper!

6. Other ways cost-effectiveness info might be used to control costs: Pt. co-pay higher for non-cost effective therapy (rx) Where does info about cost-effectiveness come from, in US; in other countries?

7. CBO report: “Can New Technology Reduce Spending? … examples of new treatments for which long-term savings have been clearly demonstrated are few…Future advances—in molecular biology and genetics, in particular—may one day offer the possibility of savings if they make curative therapies available. Continued advances in understanding the genetic origins of disease offer the credible possibility that future providers will accurately predict the health risks faced by individual patients and design therapies tailored specifically to them.” Next subject: Is this wishful thinking? How will advances in genetics impact medicine and costs? Consider genetics-based “personalized” medicine as new technology to evaluate for its cost-effectiveness.

8. What is DNA? What are bases (nucleotides) A, C, G, and T? What do we mean by DNA sequence? What are proteins? Amino acids? How is info in DNA sequence converted into protein? What is RNA, a codon, a stop codon, splicing? What is a gene? Do we get 2 copies of most genes – 1 from each parent? What is an allele? What is a mutation, e.g. CF, sickle cell hemoglobin, BRCA? What is a polymorphism?

9. How big is the human “genome”? ~3x109 bases, ~20,000 genes, in 23 segments = chromos. How does it vary between individuals? single nucleotide polymorphisms (SNPs) ~0.1%, ~106-7 insertions, deletions (indels) ~105 copy # variants (CNVs) ~102 How can variability be associated with disease or its risk? causal mutations: some are recessive (need 2 bad alleles for disease), others dominant (1 bad allele -> disease) heterozygote: 2 different alleles (at some gene locus) homozygote: mat. and pat. alleles are identical some mutations always cause disease (fully penetrant), others only in combination with environmental trigger

10. A polymorphism can be associated with a disease without causing it. How is that possible? Inheritance – during formation of egg and sperm (germ cells), one of each pair of chromosomes transmitted MP SNP 987-a b x suppose mutation x arises on a chr. carrying allele b at a nearby polymorphism SNP987 offspring that inherit x (tend to) inherit SNP987 allele b, -> disease has higher freq. in people with allele b vs allele a at SNP987 = “Founder” effect to egg Mom’s chr’s #5

11. Minor complication – chromosomes duplicate and recombine during formation of sperm and egg, which sometimes -> x being inherited with allele a MP Snp 987-a b x to egg x Snp 987- b a x Chance of recombination ~ distance between b and x

12. Some interesting details for afficionados How often does recombination occur (as a function of dist. in bases)? ~1% per Mb (106b) (per generation) How many generations does it take for probability of assoc. to fall to ½, for genes/SNPs separated by 1Mb? .99n = .5 n ~69 How long is association likely maintained? If ~25 yrs/generation, 69gen -> 1700yrs How long for genes/SNPs separated by10kb? .9999n=.5 => n ~6900 generations or170,000yrs human ancestors migrated from Africa ~200,000 yrs ago

13. Implications Nearby SNPs may not themselves be responsible for increased risk of disease, just assoc. “markers” Disease-SNP allele associations may be specific to certain ethnic groups (in which mutation arose); there may be associations with different SNP alleles if disease mutations arose multiple times Assoc. SNPs provide locational clues to causative mutations useful for research to find genetic causes

14. Homework – explore http://www.23andMe.com URL of company that provides genetic analysis direct to consumer; one founder = wife of founder of Google Go through Welcome, How it works -> lower left, genetics 101, click here to begin -> https://www.23andme.com/gen101/genes/ go through 4 sections: what are genes, SNPs, where do genes come from, phenotypes;

15. Questions we’ll discuss in class: Go back to health – what 3 kinds of tests do they offer? Learn a little more about each, then go to https://www.23andme.com/health/all/ In the carrier statuscategory, pick 2 diseases. If you are female, make one BRCA; if male, CF. Pick any second disease you are curious about. Imagine you turn out to be a carrier. How might this information affect you– now and over the next 50 years?

16. In the disease risk category, pick 2 diseases Imagine you turn out to have the high risk genotype for the first and the low risk genotype for the second. How big are the effects? How will this information affect you? In the drug responsecategory, pick Warfarin and one other drug, preferably one you have heard about. Imagine you have the same genotype as Greg Mendel’s Dad in each case. How do you respond to the results?

17. Additional homework questions (1 or 2 sentence • answers are sufficient; submit by email or paper • Do you feel you have enough information to make • an informed choice about whether you want • to take these tests? • Might your test results affect your ability to get • health insurance? Should you be free not to • reveal the results to potential insurers? • Will your test results make you more or less • likely to spend money on health in the future? • If you think you will spend more (less), do you think • this will be money well spent (saved)? • If you were the Surgeon General, would you • recommend this test for the general population?