Lecture 14- Ethnic drugs

Question 1

Objectives of the lecture?

Answer 1

• To be aware of the history of attempts to classify human populations
• To understand critiques of race science from the early twentieth century
• To understand the principles of human genetic variation and how it is measured
• To understand the principles of ‘ethnic’ pharmacogenomic drugs and genetic ancestry testing
• To be aware of the promises and pitfalls of the use of race, ethnicity and ancestry categories in genetics

Question 2

Overview?

Answer 2

• 18C racial thought
• Polygenism

– Phrenology and craniology Interbreeding

• Eugenics
• Critiques of race fixity
• Genetic differences between human populations
• Pharmacogenomics
• 18th century racial thought= how did people think about races
• polygenism= emerged in 19th century, maybe more creations of humans that is why more races

Question 3

What were the 18th century racial thoughts?

Answer 3

• Stadial theorists (Adam Smith, Rousseau)

– ‘State of nature’ – Hunting – Herding – Agriculture – Commerce

• Progressive movement through the stages was possible and inevitable
• ‘Savages’ as continuous with Europeans
• Shift from 18C 19C
• stadial theorists: Adam Smith and Rousseau
• it was believed that different populations are at a different stage in evolution (stadial theory)
• state of nature then progress to hunting and so on
• it was believed that colonisation made the progress faster
• shift from 18C and 19C= hardening of racial categories, more hardwired etc.

Question 4

What helped the progression of racial thoughts through the 19th century?

Answer 4

-the world fairs

Question 5

What is polygenism?

Answer 5

-Theory of races as separate species Phrenology

– Shape of skull corresponds to shape of brain

– Mental and moral faculties represented in certain areas

Craniology

– Samuel Morton (1819‐1850)

– Systematic skull measurements

– Internal brain capacity and facial angle

-these two pseudosciences were used as evidence for polygenism

• polygenism= more than one creation
• Polygenic arguments supported slavery and colonisation
• Australian (and Tasmanian) at bottom of racial hierarchy

Question 6

What were the aspects of human appearance important in 18th and 19th century attempts at classifying humans?

Answer 6

• shape of skull, volume of skull and face angle
• facial angle
• considered important
• Greeks and Romans were considered to be at the apex of racial development

Question 7

What were the issues surrounding interbreeding between races?

Answer 7

• Different species should not be able to interbreed
• Abundant classifications (Tschudi)
• Different species should not be able to interbreed
• Abundant classifications
• Paul Broca (1824‐1880)

– Germans + Italian fertile

– German + Aboriginal infertile

– Caucasian + Negro “Unilateral hybridity”

• the closer the racial group the more likely for the offspring to be fertile
• caucasian + negro= so when white man and negro woman= fertile if the other way around infertile

Question 8

What is eugenics?

Answer 8

• Francis Galton (1822‐1911) Hereditary Genius (1869) anticipated eugenics • Natural selection no longer applied to humans
• ‘Degeneration’ of species as sick and weak survive
• ‘Positive’ and ‘negative’ eugenics
• Claimed to address social problems of the day
• idea that have to be careful about the gene pool and do as much as possible to improve it
• bright working class people had their education paid for and moved to middle class, fear that this would remove the good genes from the working class
• but showed that smartness occurred even when removing the smart working class
• weaker and weaker as a species: shortsighted people survive etc. positive eugenics= encouragement of ideal people to have more children, negative eugenics= sterilisation, holocaust (extreme)

Question 9

What marked the end of biological race?

Answer 9

• Nazi atrocities
• UNESCO 1950 Statement on Race (Ashley Montagu, 1905‐1999)
• Race widely misused for ethnic/cultural groups
• Intelligence and personality does not vary by race
• Race mixing has no deleterious effects

Question 10

What was the UNESCO 1950 statement on race?

Answer 10

• “The likenesses among men are far greater than their differences”
• Foreshadowed Richard Lewontin (1972), The Apportionment of Human Diversity. Evolutionary Biology 6:391‐398.
• Contemporary science still grappling with questions of difference between ‘population groups’

-or is it that we are ignoring race and perpetuating health issues in subsets of populations because we don’t look into it

Question 11

What are the modern genetics of biological differences?

Answer 11

• Random mutations and natural selection cause changes in genes over time
• History of human population movements result in genetic differences between population groups
• Differences in frequency of alleles (e.g. 40% in group A, 70% in group B) and some unique alleles
• Africa most diverse by a long way
• Africa is the most genetically diverse by far eg. Australians= isolated fro 10 000s of years, enough to develop phenotypic differences

Question 12

What are pharmacogenomics?

Answer 12

• Tailoring drugs to individual genetic makeup
• Major part of ‘individualised medicine’
• The re‐emergence of biological race?
• Self‐identified race as a ‘place‐holder’ on the road to individualised medicine
• Scepticism about how long ‘place‐holder’ will remain in place
• cancer drugs are a poster child, some drugs can be super successful but in a small subset of the people
• is it also a back door for re-emergence of biological race
• race is a proxy, it is an indication

Question 13

What is Bidil?

Answer 13

-Bidil, the first ethnic drug

• 1980s V‐HeFT I : hydralazine/isosorbide dinitrate beneficial in heart failure
• 1987: patent for H/I combination (expires ’07) • 1997: FDA rejects application for Bidil
• 1999: Reanalysis shows mortality reduction for blacks

Question 14

What are the criticisms of Bidil?

Answer 14

• Original trial small (49 African American subjects in H/I arm) • A‐HeFT trial only had African Americans and only used placebo not standard treatment
• Just about extending a patent and creating a new ‘ethnic’ drug market that will increase health care cost for African Americans.
• Misplaced way of FDA showing that it cares about health disparities
• “There is distrust of the health provider community by African‐Americans, some of it justified. So we have to overcompensate in order to make people comfortable in minority groups with participating in clinical trials.These folks were able to pull it off and I am going to give them some points for that.”

Question 15

Conclusions?

Answer 15

• There are genetic differences between ancestral populations that have implications for health and phenotype
• But race as a ‘placeholder’ on the road to individualised medicine is hazardous
• Vested interests in the past led to abuse of biological race: colonial/national power over ethnic minorities
• Today’s vested interests: identity, access to special benefits, economic