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Goodman, et al. Chapter 9
Why Human Variation is NOT Racial
Sickle Cell Disease: Not for Blacks Only 1
• Most of us have heard of the disease called “sickle cell disease” (SCD) or “sickle cell anemia” (SCA).
• Most often we tend to associate this disease with African Americans. But as the title of this chapter denotes, SCD
is more widely spread geographically.
• In this chapter we will review the consequences of SCD, both genetically and physiologically, make a connection
with another disease, malaria, and discuss where SCD is found.
• There is a single evolutionary stressor responsible for the prevalence of SCD in humanity: malaria.
• But, there are many evolutionary responses to malaria; the sickle trait is only one. A few other examples:
• Hemoglobin C and hemoglobin E variants, which exhibit mild symptoms but provide some protection against
malaria.
• Ovalocytosis causes a more rigid RBC, but also facilitates a response called “sequestration” in which the
malaria adheres to a glycoprotein called CD36 (think fly paper effect).
• Alpha ()-thalassemia and beta ()-thalassemia are the result of defective globin production which can cause
the destruction of red blood cells (RBCs)
• Glucose-6-phosphate dehydrogenase deficiency (G6PD) deficiency, which affects an energy metabolic
pathway.
• Duffy RBC antigen, the presence of which appears to block malaria from entering RBCs.
• So given the number of genetic adaptations to malaria, it is immediately obvious this parasite is a major killer.
Sickle Cell Disease: Not for Blacks Only 2
• Medical history: The discovery of strangely shaped RBCs
• The first discovery of “sickled” red blood cells was over 100 years ago.
• It was first discovered in people of African descent so it was labeled as a “negro blood” disease.
• It became typed as such, but was not the only disease to be so labeled.
• A range of diseases of the heart, ovarian cysts, and so forth were allocated to racial types.
• In part this was set against a backdrop of colonialism
• As Westerners conquered indigenous peoples they had to maintain residence in these regions. So many
Europeans died that these geographic regions came to be known as the “graveyards of mankind”.
• A corollary of this mindset was that Europeans were particularly prone to “diseases of civilization”: heart
disease and cancer, in particular.
• As to SCD, there is a high frequency of this trait in W. Africa, but this does not mean it is a “black disease”.
• The field of hematology (study of the blood) incorporated new technologies, such as the microscope in the early
years of the 20th century.
• The first finding was that not all RBCs are shaped the same.
• But, in these early years of research, the concept of race-specific diseases remained deeply embedded in
science.
• When SCD was discovered in Europeans researchers went looking for evidence of the patient’s African
ancestors.
• This insistence on an “admixture explanation” slowed the scientific understanding of this disease, caused
erroneous diagnoses, and emotionally charged the discussions of this disease (given the “racial paradigm”
of the day).
Sickle Cell Disease: Not for Blacks Only 3
• What is sickle cell?: Genetics and physiological consequences
• Most phenotypic variation is a complex interaction between the environment and an array of gene variants.
• Polygeny and pleiotropy explain the combination of interactions that can occur if traits are complex.
• Polygenic traits are traits resulting from two or more gene loci. When several loci act to control a trait,
many different genotypes and phenotypes can result.
• Pleiotropy occurs when an allele (single gene locus) affects more than one trait.
• Both polygeny and pleiotropy can occur at the same time.
• The effects of polygeny and pleiotropy are that it is hard to identify the causes or to state that x causes y.
Sickle Cell Disease: Not for Blacks Only 4
• What is sickle cell?: Genetics and physiological consequences (continued)
• Sickle cell is a Mendelian trait (it is one of the “x causes y” traits).
• So, in order to understand the context of Mendelian traits, we are going to do a VERY short review of genetics.
• Austrian priest Gregor Mendel (1822-1884) carried out an extensive series of experiments in plant breeding,
using pea plants now basic to our understanding of genetic inheritance.
• Mendel’s experiments demonstrated a pattern of inheritance unknown before. He deciphered two laws:
• One of them was the Mendel’s law of segregation: Mendel showed that genes do not blend together in
an offspring, but instead genes are discrete (separable, aka segregated into chromosomes)
• Mendel’s law of independent assortment states that the segregation of any pair of chromosomes does
not influence the segregation of any other pair of chromosomes.
• Confused? I urge you to create your own genome of 3 pairs of cards (aces, twos and threes). Only use two
suits. Then practice.
• It took until the 1950s to have the specific structure of inheritance identified and described (DNA/RNA) by
Watson and Crick (Mostly based on the uncredited work of Rosalind Franklin).
• The DNA molecule provides the codes for biological structures and the means to translate this code.
• DNA provides information for building, operating, and repairing organisms.
Sickle Cell Disease: Not for Blacks Only 5
• What is sickle cell?: Genetics and physiological consequences (continued)
• Genotypes and phenotypes
• For some genes, there is more than one version in their coding. This condition is called polymorphism
(meaning many shapes).
• The actual code for a specific gene is called its genotype.
• The variants are called alleles. Sometimes an allele is expressed by making a different version of the
protein or blocks the making of a protein, and so on.
• When a person receives two different versions of the gene on their two chromosomes, this is called
heterozygosity (they are heterozygotes).
• If the person receives two genes that are the same this is homozygosity (they are homozygotes).
• Of course the exception is with the sex chromosomes of humans.
• Males only have 1 copy of the X and one of the Y.
• The Y chromosome is thought to be evolutionarily a “shrinking X”; a X chromosome
destined to shrink and shrink (this idea is called the “shrinking theory”).
• Good news: A comparison of humans with other primates shows there has been no
shrinking in at least 6 million years.
• Females have 2 copies of the X, but no copy of the Y.
• This is why you often hear of X-linked traits or Y-linked traits.
• The term for what the organism looks like as a result of this gene (or its interaction with other genes) is called
its phenotype. The phenotype is also affected by the environment.
• The relationship between genotype and phenotype is affected by the relationship between the two alleles present
at any locus.
Sickle Cell Disease Not for Blacks Only 6
• What is sickle cell?: Genetics and physiological consequences (continued)
• DNA (deoxyribose nucleic acid): The genetic code
• The DNA molecule provides the codes for biological structures and the means to translate this code (codes for
proteins).
• The DNA molecule resembles a ladder twisted in a helix shape.
• Ladder rungs represent chemical units called bases (also called nucleic acids or nitrogenous bases).
• There are four possible types of bases: A (adenine), T (thymine), G (guanine), and C (cytosine).
• Chemical bonds: A is complementary to T while G is complementary to C.
• The backbone is made of a sugar-phosphate structure.
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It is to this structure that the bases are attached.
The sugar in DNA is called deoxyribose (meaning a lack of an oxygen; it is a variant of ribose (a 5carbon sugar).
DNA groups amino acids together to make proteins.
• There are 20 amino acids found in humans, some are made in the body, others are digested (scavenged from
other living organisms).
• DNA actually serves to bring the 20 amino acids together in the proper order needed for a specific protein.
• To do so, the DNA is combined into triplets (such as ATC or ATT) this means there are 64 (43) triplets!
• These triples are called codons. There are duplicates for some amino acids (64 codons, but only 20 amino
acids).
• Errors occur (mutations). Some are errors called “point mutations”, when a single nucleic acid (A,T,C, or
G) is wrong.
• Some point mutations are “silent mutations” because they end up coding for the same amino acid as
the original.
• But, some cause a different amino acid to be brought in. This happens in SCD.
Sickle Cell Disease: Not for Blacks Only 7
• What is sickle cell?: Genetics and physiological consequences (continued)
• Sickle cell is a variant of the RBC that can be seen through the microscope.
• For SCD there is little variation in the phenotypic expression.
• Further, it is a type of phenotype that exhibits penetrance (the effect “shows through“) or in other words, if
you have the genotype you will exhibit the phenotype (disease).
• The mutation for SCD is found on chromosome 11, the section of DNA which codes for the 6th amino acid in a
146 amino acid protein is wrong.
• The nucleic acid A became the nucleic acid G due to a point mutation.
• This caused the amino acid valine to substitute for the correct amino acid
guanine.
• If one copy of the gene is mutated you get sickle cell trait, if both copies you have
SCD.
• So which protein does this 146-amino acid chain make?
• It makes a protein that is part of hemoglobin.
• Hemoglobin is composed of 4 “arms”; two are labeled as alpha ()-chains
(red) and the other two as beta ()-chains (blue).
• Additionally, each arm carries a heme (green).
• This non-protein structure is where iron attaches to oxygen it collects.
• The red color of blood is a result of the heme attaching to oxygen.
• The normal variant of the hemoglobin is designated as HbA. (We also normally retain a bit of fetal
hemoglobin form called HbF). The sickle cell variant is designated as HbS
Sickle Cell Disease: Not for Blacks Only 8
• What is sickle cell?: Genetics and physiological consequences (continued)
• HbS is a Mendelian trait caused by a SINGLE change in an amino acid selection. As you can see on the right, the
sickle cell shape is different phenotype.
• HbS causes a number of physiological issues.
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Reasons for blood flow blockages (very painful):
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The difference in shape (sickle) causes these mutated RBCs to get stuck.
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As they are more rigid and more “sticky” these characteristics also cause them to get stuck.
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Also the HbS does not carry oxygen as easily.
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The symptoms most commonly liked to SCD are anemia, joint pain, and damage to organs such as the lungs,
kidneys and eyes.
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If both parents are “carriers” of the sickle cell trait, each time they have a child there is a 1-in-4 chance their child
with be SCD, 2-in-4 chance each child will be a carrier, and 1-in-4 chance their child will have only HbA genes.
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Sickle cell is an example of a balanced polymorphism.
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The cost is high: SCD, but the cost of HbA is also an issue, no resistance to malaria.
Best to be a carrier (heterozygote).
Sickle Cell Disease: Not for Blacks Only 9
• The sickle cell story: Unnatural history of the mosquito, humans, and malaria
• Let’s begin with an overview of the evolutionary stressor: malaria.
• Malaria kills and when it doesn’t it is still a “nasty” disease.
• Each year at least 500 million cases are reported, at least 1 million people die. Children under the age of 5
years are the most vulnerable to malaria.
• In my personal life, I went from studying malaria in the lab to having it when I did field research in the
Solomon Islands.
• There are actually a number of different species of malaria:
• Generally one hears that there are four species of Plasmodium infect humans and cause malaria
(Plasmodium falciparum, P. malariae, P. ovale, and P. vivax).
• Plasmodium knowlesi is found only in SE Asia and has been misdiagnosed as P. malariae. Problem is
that it is more deadly.
• Rarely these also have been infectious: P. inui, P. cynomolgi, P. simiovale, P. brazilianum, P. schwetzi
and P. simium
• FYI: P. vivax was probably present in the New World prior to Western contact.
• Symptoms of malaria (Source: CDC):
• Symptoms include fever and flu-like illness, including shaking chills, headache, muscle aches, and tiredness.
• Nausea, vomiting, and diarrhea may also occur.
• Malaria may cause anemia and jaundice (yellow coloring of the skin and eyes) because of the loss of red
blood cells.
• Infection with one type of malaria, Plasmodium falciparum, if not promptly treated, may cause kidney failure,
seizures, mental confusion, coma, and death. This form is responsible for cerebral malaria.
The Malaria Life Cycle
(Not pictured)
Sickle Cell Disease: Not for Blacks Only 10
• The sickle cell story: Unnatural history of the mosquito, humans, and malaria
• Malaria has a life cycle that takes advantage of two species; both become hosts for these parasites.
• In humans the Anopheles mosquito infects the human when it comes for a blood meal
• And the mosquito is infected in turn when the blood of the human is infected.
• Here is an excellent short tutorial on malaria (TESTABLE).
• So why is malaria so often found in association with humans? Farming!
• In the Middle Ages it was thought malaria was caused by bad air (thus the name of mal aria)
• Today we recognize malaria is the result of contact with infected mosquitoes of the genus Anopheles
• One suggestion is that malaria became a significant disease among humans only after we became farmers.
Distribution of Anopheles species
(Not pictured)
Sickle Cell Disease: Not for Blacks Only 11
• The sickle cell story: Unnatural history of the mosquito, humans, and malaria
• All bets were off’ when humans shifted from the foraging (aka hunting-gathering) lifestyle to farming (aka
agriculture).
• Disease in hunting-gathering populations
• The two most common types of infectious disease in hunting-gathering populations are due to parasites
(lice and pinworms) and zoonoses -- diseases transmitted from other animals to humans (malaria, sleeping
sickness, tetanus, and schistosomiasis).
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Most diseases are endemic (occurring at relatively low, constant rates) in hunting-gathering populations.
An endemic pattern shows a low but constant rate; hunting and gatherer populations do not have
epidemics (high rates, rapidly spreading) or pandemics (widespread epidemic) for 2 reasons: Small
population size & mobility.
• Infectious disease in agricultural populations
• But farmers set themselves up for malaria infestations (as well as many other infectious diseases):
• Sedentary populations are more likely to engage in long distance trade.
• They create more favorable conditions: permanent shelters bring rodents, garbage and polluted water
• Alteration of the landscape by horticulture, animal husbandry and agriculture exposed humans to new
diseases.
• Improvements in cooking technology, especially pottery, did allow for longer cooking times (more
healthy), but also may have encouraged growth of some bacteria, as did storage
• Regular contact with domesticated animals exposed humans to additional infections
• The greater the population density the easier it is for infectious diseases to spread.
An interesting article you might read is The arrow of disease.
Sickle Cell Disease: Not for Blacks Only 12
• What can we do to prevent malaria?
• One of the best ways to resist malaria is one of the oldest -- genetic adaptation.
• Some of the first work on the link between SCD and malaria was done by Frank Livingstone, an
anthropologist.
• He went to Liberia to study the relationship between SCD and child growth only to find no-one in his
study group had the trait! But malaria was everywhere.
• His work showed that malaria was too recently introduced to this region for any genetic adaptation to
develop.
• Another researcher, famous for his work on vitamin C, as well as on malaria was Linus Pauling.
• He, and his colleagues, determined that SCD has a molecular basis, the alternation of hemoglobin, which
they reported in a journal article called Sickle cell anemia: A molecular disease
• He and others thought that HbS stopped malaria from penetrating the RBC. Recent research shows this to
be incorrect.
• Malaria CAN still infect RBCs just fine.
• The protection is actually that HbS causes more carbon monoxide to be produced which decreased the
ability of malaria to invade the brain.
• Great, but what if you do not have a genetic advantage?
• Take prophylactic dose of anti-malarial drug 4-6 weeks prior to entering a malaria zone.
• DEET (di-ethyl toluamide) is your friend.
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Long sleeves and socks and whatever is needed to cover exposed skin.
• Sleep under a net and use screens and other tools that block out mosquitos from the home.
• Avoid places and times of high mosquito activity.
Sickle Cell Disease: Not for Blacks Only 13
• Race and sickle cell
• Sickle is the result of human history and evolution.
• Race has NOTHING to do with this genetic adaptation. There is no “disease of the negro blood”.
• In 2010, an article in Nature confirms the “malaria hypothesis” as the explanation for the distribution of the sickle
cell trait.
Standards and race: Iron deficiency
• Goodman et al. suggest there are two ways that race gets into medicine:
• Informal, individual knowledge that filters the medical personal’s questions into preconceived ideas about
illness. These stereotypes inform, even if not based on science.
• Science also sets up categories and makes them formal. Remember our earlier discussion of reification? It’s
back!
• The example of anemia provides an example of a cautionary tale.
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Stanley Garn, Joseph Birdsell, and Carleton Coon represent the last generation of anthropologists to had
strongly to the concept of race as reality.
• Together they published a book, Races: A study of the problem of race formation in man, in 1950.
• Stanley Garn wrote a book called, Human races, in which he described several levels of races
• Geographical races: those which live in the same area but are distinctly different.
• Local races: live in the same are but are different.
• Micro races: those which share geography and culture but are still distinctly different.
• Joseph Birdsell tried to racialize Australian aboriginal populations in his later work.
• Carleton Coon, in his book (1962), The living races of man, argued for 7 geographic races (up from
5).
Garn also did work on anemia and suggested there were different cut-off values for blacks and whites.
• Work by Jackson and Jackson determined the original data is not correct.
• The result? Many continue to use erroneous values for blacks, causing diagnostic errors.
Sickle Cell Disease: Not for Blacks Only 14
• Race and athletic performance (Joseph Graves)
• Graves is well-recognized for his work on the history of racism.
• We actually met Graves in an earlier lecture that I presented from his book, The emperor’s new clothes.
• In this interview Graves reviews our perceptions about athletes.
• Is there any link between race, genes and athletics?
• Many Americans believe that there is some special athletic ability to be found only in African Americans.
• This explains the presence of so many black athletes in running and basketball, for instance.
• One prevalent stereotype, for instance, is that “blacks have an extra muscle in their legs that lets them run
faster”. This one shocked me; the pure ridiculousness of it.
• The irony of this presupposition is even more poignant if one knows that at one time the opposite stereotype
was common: that blacks are physically inferior and destined to die out.
• This idea was called the “extinction hypothesis” proposed by Frederick L. Hoffman
• In his 1896 publication, Race traits and tendencies of the American Negro, Hoffman stated that the
Metropolitan life tables showed that American blacks were not insurable as they were destined for
extinction.
• Rather that discuss the social issues that resulted in the differing mortality rates, he stated there were
innate reasons for the biological inferiority of blacks.
• Are there no differences in the sprinting ability of a group adapted to the Arctic cold or to the Tanzanian
savannah? Of course, but remember these issues around discrete traits version continuous ones? And the
discussion about complex traits (polygenic and pleiotropic)?
• Winning at athletics has some genetic contribution, some environmental, some to do with training.
• If you ever get a chance, watch The perfect runner so you can the complexity of this issue.
Sickle Cell Disease: Not for Blacks Only 15
• Race and athletic performance (Joseph Graves) (continued)
• Superior at athletics means inferior in other areas?
• Graves reminds us that if an African American walks onto
campus, s/he is first expected to be there on an athletics
scholarship.
• This example is another positive stereotype (remember this
term from earlier in the quarter?). Who does not want to be
considered athletic?
• In fact, Graves is often approached on campus himself and
asked if he is the football or basketball coach, and not asked
if he is the leading scholar he really is.
• He reminds us that positive stereotypes hid the flip-side: There is an assumption that those who are
athletically talented lack intellect. Has anyone never heard the insult “dumb jock”?
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He reminds us that the 6 o’clock news is most likely to show African Americans as athletes (often ones in
legal trouble) or in the entertainment business (comedy, dance, and so forth).
• Again, the danger is in the narrowness of the portrayal. Other examples:
• How many times in the last year have you seen American Indians portrayed as other than drunks or as
historical figures?
• Or Mexican-Americans as other than illegal immigrants?
• Or strong women who are also home-makers?
Robert Merton discusses stereotyping by attitude (prejudice) and action (discrimination).
Sickle Cell Disease: Not for Blacks Only 16
• Race and athletic performance (Joseph Graves) (continued)
• Which groups have dominated sports?
• In the 1960s it was thought that African Americans were fast so they were sprinters, but Europeans and
Middle Easterners were allocated the spots on long-distance teams.
• In the beginning years of professional basketball it was Jewish Americans who dominated the pro teams
(because of their “artful dodger” characters)
• At the turn of the 20th century, the Irish dominated boxing
• Tennis and golf remain predominantly upper class Euro-American sports, even with the presence of Tiger
Woods and the Williams sisters.
• Why are have there been shifts in who dominates which sport?
• Obviously it not based on race. Different groups, at times they are economically and socially disadvantaged,
see sports as a way out and up
• This use of sports as a mechanism of social mobility, along with a study of the historical context of sports,
explains the differences.
• This is nurture, not nature, issue, to the greatest extent.
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