CURSE AND

BLESSING OF
THE GHETTO
By Jared Diamond

TAY-SACHS DISEASE
Tay-Sachs Disease is named after two
physicians--British ophthalmologist W. Tay,
and New York neurologist B. Sachs. They
independently recognized the disease back in
1881 and 1887, respectively.

TAY-SACHS DISEASE
Tay-Sachs Disease is a
rare, incurable, and
unpreventable autosomal recessive genetic disorder
which is caused by Hexosaminidase A (HEXA) deficiency
in lysosomes. Lacking this enzyme causes excessive
accumulation of the fatty substance called GM2
ganglioside in nerve cells, particular in the spinal cord
and brain.

SYMPTOMS
Symptoms appear 3-6
months after birth
Loss of muscle
strength and control
Convulsions/Seizures

SYMPTOMS
Increased startle
reaction
Excessive drooling
Enlargement of head
Loss of eyesight

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By the
childs 3rd
birthday, if
hes still
alive, his skin
will turn
yellow and
hands pudgy.
Most likely
hell die
before he is
4 years old.

1 in 400,000
Births around the world

1 in 3,600
Births among descendants of Eastern
European Jews (Ashkenazim)

WHY IS TAY-SACHS
DISEASE MOST COMMON
AMONG ASHKENAZIM
PEOPLE?

10

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HISTORY

2000
years ago

Due to violence
Peacefully
Settled in
Mediterranean
France and
lands
Germany
Yemen
India

Lived in virtually
confined towns
Crowded ghettos

From Israel
Jews spread

Persecution drove
Jews out of Western
Europe

Spanish Jews (Sephardim) -> lands

around Mediterranean
France and German Jews
(Ashkenazim) -> East to Poland ->
Lithuanian and Western Russia

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HISTORY
End of
19th
Century

Lowest TB deaths among

Ashkenazic parents of
Tay-Sachs children

Waves of murderous anti-Semitic

attacks drove millions of Jews out
of Eastern Europe -> US most

1972

Present

13 million Jews today

- 3/4ths are Ashkenazim (descendants
of Eastern European Jews - most
risks of Tay-Sachs)

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4 Hypotheses

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1st Hypothesis
Mutation as fast as existing copies disappear
New copies of the gene arises as fast as the existing
copies disappear with the death of the affected
individual
Implies mutation rate of at least 1 per 36,000 births

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1st Hypothesis
Why not?
1 in 3,600 is a frequency far above any human gene
No precedent for one particular gene to mutate much
more often in one ethnic population compared to
others

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2nd Hypothesis
Acquiring the Tay-Sachs gene from others who already
had the gene at high frequency
According to Arthur Koestlers The Thirteenth Tribe,
Ashkenazim are
Not Semitic people
Descendants of Khazar--a Turkic tribe who converted
to Judaism

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2nd Hypothesis
Why not?
No good evidence to support.
Doesnt explain why it wasnt eliminated after 1,200
years
Doesnt explain how the Khazar had it in the first place

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3rd Hypothesis
The founder effect and genetic drift
Applicable for small population
New copies of the gene arising fast due to genetic
accidents

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100

Couples in a new island

1 in 1,000,000
Frequency of having a rare gene

1 in 200

Frequency of having the rare gene in a the

new population

20

100

in a new island

1
Man with the rare gene has lots of kids

99

Men has few or no child at all

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98 / 333

Has the Tay-Sachs gene

333 from 1
Couple who migrated to US and had

13

Children

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3rd Hypothesis
Why not?
Ashkenazim may have been a quite large population
Ashkenazim communities are widespread; the drift
will be inconsistent
Natural selection had thousands of years to restore
the gene frequency to normal

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Molecular Biologists VS Genetic Accidents

Along the stretch of the affected DNA, several different
sites of mutation have been identified and 2 of them occur
more for non Ashkenazim
It is very unlikely to pump up the frequency of the
same gene twice the population

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Molecular Biologists VS Genetic Accidents

Tay-Sachs is one of the 10 genetic diseases of
Ashkenazim people
Gauchers, and Niemann disease also result from
accumulation of 2 other fatty substance and defects in
2 other enzymes similar to HEXA

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4th Hypothesis
The Tay-Sachs gene is both a curse and a blessing
Tay-Sachs, Gauchers, and Niemman, kill individuals
who have 2 copies of the faulty gene but help people
who only have 1
Ex: Sickle cell (Africa) VS Malaria

Natural selection doesnt eliminate

the gene because there are more
Heterozygous individuals who will
survive compared to Homozygous
ones

26

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1 / 306
Of grandparents with TS gene died from TB

20%
Of the causes of all deaths was TB

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4th Hypothesis
Where is the Blessing?
The Tay-Sachs gene was 9-10% more frequent in
Austria, Hungary and Czechoslovakia compared to
Jews from Poland, Russia, and Germany
Austrians and Hungarian Jews were overrepresented
in the 1904 TB report on patients born in Europe
between 1860-1900

Where the TB is the biggest threat,

natural selection produces the
biggest response

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WHY IS THE GENE COMMON JUST

IN ASHKENAZIM AND NOT IN
NON-JEWS EXPOSED TO TB?

30

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PREVALENCE OF THE TS GENE IN

ASHKENAZIM
Eastern European Jews were businessmen
They were forced to live in the crowded ghettos where
TB thrived
High death rate = Higher emigration rate
Jews do not emigrate and were always in the ghettos
because of their business

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CONCLUSION
TB resistance is the only plausible
hypothesis yet proposed
Evidences are still speculative for the
4th hypothesis
Tay-Sachs disease is both a product of
Natural selection and Historical events

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THANKS!
Any questions?