Harper\'s Magazine - 03.2020

ANNOT

36 HARPER’S MAGAZINE / MARCH 2020

ANNOT

OUT OF

The legacy of colonialism threate

By Oscar

Fifteen years earlier, scientists at a medical center in Dallas had begun searching
for people with mutations in a gene known as PCSK9. Previous studies had found
that a mutation that activated this gene leads to excessive cholesterol in the blood,
causing waxy, yellow clumps to accumulate under the skin. When a mutation
inhibited the expression of PCSK9, however, cholesterol levels were lower, even
in people with lifestyle risks such as smoking cigarettes or eating high-fat foods.
For researchers working in the emerging field of genetic medicine, PCSK9 was a
promising lead. If they could find people with the inactive mutation on both
copies of the gene, they might be able to develop a safe medication to prevent
coronary heart disease, which is responsible for one in eight deaths in the United
States. But the search would not be easy. The inactive PCSK9 mutation was most
common in people of African ancestry. In the available data, scientists could find
only one person who carried a double inactive mutation of PCSK9: a thirty-two-
year-old, African- American aerobics instructor in Dallas. As they had hoped,
the instructor had astoundingly low cholesterol levels—around one seventh the
amount of the average adult. A year later, researchers in South Africa identified
another case—a twenty-one-year-old woman, who was in a maternity ward in
Zimbabwe—that confirmed the Dallas findings. Studying her genome led to the
development of two effective drugs for managing cholesterol.

The reason African genomes are so important in drug discovery has to do with the history of human evo-

lution and migration. According to the “Out of Africa” model, when small groups of Homo sapiens began

to leave the continent around one hundred thousand years ago, they passed through a population bottleneck.

The migrant communities had far fewer people with whom they could reproduce, which greatly diminished

the gene pool in these geographically dispersed populations. To this day, people of African descent—

whose ancestors did not pass through the population bottleneck—carry more genetic diversity than

people of non-African ancestry. African genomes, therefore, offer researchers a depth of genetic information

that non-African genomes simply don’t have. In the years after the PCSK9 studies, which over-sampled

people of African descent to increase the chances of finding the relevant mutation, many prominent ge-

neticists realized that progress in the field would slow dramatically unless general sampling practices were

expanded to include African ancestral groups. Genetic databases would need to be radically diversified.

In 2014, Deepti Gurdasani, a genetic epidemiologist at the Wellcome Sanger In-
stitute in England, coauthored a paper in Nature on human genetic variation in
Africa, from which this image is taken. A recent study had found that DNA from
people of European descent made up 96 percent of genetic samples worldwide,
reflecting the historical tendency among scientists and doctors to view the male,
European body as a global archetype. “There wasn’t very much data available from
Africa at all,” Gurdasani told me. To help rectify the imbalance, her research team
collected samples from eighteen African ethnolinguistic groups across the
continent—such as the Kalenjin of Uganda and the Oromo of Ethiopia— most of
whom had not previously been included in genomic research. They analyzed the
data using an admixture algorithm, which visualizes the statistical genetic differ-
ences among groups by representing them as color clusters. The top chart shows
genetic differences among the sampled African populations, in increasing degrees
of granularity from top to bottom, and the bottom chart shows how they compare
with ethnic groups in the rest of the world. The areas where the colors mix and
overlap imply that groups commingled. The Yoruba, for instance, show remarkable
homogeneity—their column is almost entirely green and purple—while the
Kalenjin seem to have associated with many populations across the continent.