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I actually would like to take this
occasion to praise and thank the TAs.

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We've been teaching this course for
about a dozen years and we've had

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some really excellent groups of TAs,
but this year's crop is really off

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scale, really outstanding.
And we're all very grateful.

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[APPLAUSE] You know their names.
I won't go through them all.

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But the fact of the matter is
these TAs teach this course because

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they're told to teach the course,
and at the same time they're doing

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all their thesis research, so
they end spending about 168 hours

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a week on various kinds of work.
So it's not a natural thing for

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them to spend an enormous amount of
time, as they have been this year,

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really just off scale
extraordinarily good.

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Here they are, Winston,
Susan, Michelle, Sara, Divia,

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Jim, Sydney, Yasmine and
Cha. So thank you all.

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At the same time, I'd also
like to thank Claudette

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Gardel who runs this thing.
This is a large undertaking,

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believe it or not, with
almost 350 students enrolled,

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but it's moved seamlessly and
without any problems this year for

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which many of us are very grateful.
So, thank you Claudette. I'm going

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to spend today trying to
broadcast into the future,

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forecast into the future I should
say, about where all of what we've

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talked about this
semester is taking us.

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Where is it going to get it us in
terms of where we're going to be ten

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or twenty years from now and what
you're going to be in the middle of

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ten or twenty years from
now as you begin to move,

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as it will happen surely, as
day follows night, into midlife.

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Imagine that. When you're
35 or 40 this will happen.

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And in order to do so I just want
to go back 125 years or so to give

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you a feeling for what the
history of biology has been like,

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some of it, since the
end of the 19th century.

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Just to give you a little flavor for
what can happen to biology if things

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aren't done right. Charles
Darwin had a cousin named

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Francis Galton. He was
knighted by the Queen and

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called Sir Francis Galton.
And he was an early pioneer in

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statistics. And he coined
the term eugenics. And,

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as you may note, eugenics
is simply the science of

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trying to use genetics
to bread better livestock,

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better plants, and ultimately
maybe to breed better human beings.

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And we humans have been doing
eugenics on plants and livestock for

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at least 10,000 years. That
is to say we have continually

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been selecting out the best of the
breed as the progenitors of the next

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generation of the breed. And
in that way corn, which was

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originally this large when it was
grown 5,000 years ago in Mexico,

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the cobs have now become
this large and quite tasty.

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And all of that is through selective
breeding. But in the last half of

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the 19th century, inspired
by Darwin and subsequently

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by Mendel's work on Mendelian
genetics, a whole science of

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eugenics grew up in this country
which included not only the

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improvement in the quality of
livestock and plants but also

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improvements in the gene pool
of humanity. There was a strong

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conviction that genes were directly
responsible for all kinds of

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physical traits, as well
as mental and psychological

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traits. There was a
strong belief that some

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races were superior and other races
were inferior because of genetic

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gifts or genetic deficits. And
this included as well within

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races, however one defined them,
different ethnic groups. There was

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a firm belief that science could
ultimately solve a lot of social

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problems including urban violence,
labor unrest, manic depression,

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schizophrenia and even
mental retardation.

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And the eugenicists, as
they came to be known,

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came to believe that the
problems of the world, alcoholism,

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poverty, prostitution, criminality,
feeblemindedness, chess playing

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ability, tendency to
commit industrial sabotage,

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that was big in the beginning of
the 20th century when the unions were

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coming into power, they were
all associated with one or

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another rather penetrant
Mendelian allele.

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A well known geneticist named
Davenport, who subsequently was

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associated with an unnamed
university up Mass Ave.

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studied various ethnic groups and
races and concluded that on the

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basis of genetics the Germans
ranked highest in quality such as

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leadership, humor, generosity,
sympathy and loyalty.

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Italians and Irish ranked
lowest in most of these traits,

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he was lucky he survived in this
town since together Italians and

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Irish, I think encompass
70% of the population.

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British were lowest in two of
the traits. Irish were highest in

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suspiciousness. Jews were
highest in obtrusiveness,

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whatever that is. And all of these
things were said to be genetically

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templated. And so at the beginning
of World War I IQ tests were first

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instituted in this country during
the draft in order to determine who

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was genetically fit to serve
and who was below standard.

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And using IQ tests, which
were implemented in great

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numbers and throughout the
society in the 1920s, a well known

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geneticist named Goddard
discovered that 80% of Jewish,

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Hungarian and Polish immigrants,
as well as Italian and Russian

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immigrants were mentally
defective or feebleminded,

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and that these traits, these
mental defects in 80% of these

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groups were transmitted as
regularly and as surely as the color

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of hair or eyes. I'm not
making up fairy tales now.

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I'm telling you what's happened in
our history. In the 1920s there was

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a Eugenics Record Office in this
country which existed for the next

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twenty years, an American Eugenics
Society which has 1200 people,

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and J.H. Kellogg of Battle Creek,
Michigan, you know how he made his

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money, don't you? Cornflakes.
He founded a Race Betterment

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Association whose intent was to
better the gene pool of the American

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population through selective
breeding. By 1928 there were 376

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college courses taught across this
country on the subject of eugenics,

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i.e., how to improve the human
race by beginning to breed more

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fit individuals. And so
when the Nazis came to power,

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as they did in 1933 in Germany,
they had much to draw from.

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In fact, most of their scientific
rationale, to the extent they had

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any, didn't come from Germany,
it came from eugenicists in the

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United States. And so
they began to look amongst

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their society for people
who were useless eaters,

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i.e., they consumed food but didn't
produce, they lived lives not worth

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living, the elderly, the
chronic poor, the crippled and

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the misfits. And
they began involuntary

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sterilization. So, people
who were regarded as

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genetically less fit were sterilized.
By the time the Nazis finished

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their 12 years in power, 400,000
people had been sterilized

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in Germany because for one or
another reason they were regarded as

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somehow defective. And as
the Second World War made

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resources more tight, they
just did something much simpler,

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they just euthanized people,
they just killed them if they were

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regarded as in one way or
another genetically defective.

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In fact, my father had a first
cousin who around 1936 or so was

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gassed because he had
a bad stuttering defect.

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So, this is all things that
really happened to people.

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As a consequence of all of this
eugenics, by 1924 Immigration Act

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was passed which severely
circumscribed the amount of people

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immigrating into this country
because the immigrants were widely

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viewed as diluting and
contaminating the American gene pool.

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And this probably, well,
this undoubtedly had a

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devastating affect on this country
which we'll never really be able to

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know because the truth of the
matter is that to the extent we have

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economic and scientific
robustness in this country,

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it has come, for the last century,
year after year, generation after

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generation from the immigrants
who come to this country,

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not people who were here
three, four, five generations.

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It's the immigrants who
brought in the new ideas,

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the energy, the power, and I
venture to say that if I were

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to ask what fraction of you are
first generation Americans the

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number would be pretty high,
right? But in 1924 that was for a

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while stopped simply because people
coming into the country were viewed

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as genetically less
than acceptable.

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By 1940 thirty states had compulsory
sterilization laws in this country,

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i.e., people who were deemed to
be genetically less gifted were

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sterilized against their will.
60,000 of those sterilizations were

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performed in this country. And
the eugenics moment gained more

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and more adherence. What shut
it off ultimately was what

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happened in World War II where
six million Jews were killed,

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along with probably five or six
million Slavs and other races who

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were deemed, and gypsies, there
were probably half a million

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gypsies killed by the Nazis,
different groups of people who were

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deemed to be genetically less
deserving of living and genetically

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less likely to be productive
and useful human beings.

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And were it not for World War
II, it's quite plausible that the

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eugenics movement would have
continued to grow and that today,

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when we talk about genetics, much
of it would be referred to a belief

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that somehow we can determine
people's phenotype and genotype and

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that we can predict how useful or
useless they're going to be on the

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basis of our insights into genetics.
And this ideology of genetic

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determinism, I say it had a great
decline, this is the phrase we use,

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genetic determinism, i.e., to say
that an individual's life course is

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strongly dictated
by his or her genome.

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These are her alleles. You
heard a lot about the alleles

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last time from Eric. But
genetic determinism is once

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again coming to the forefront.
Why? Because now, for the first

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time, we actually have a
science of human genetics.

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When all of this other stuff was
going on 50 and 100 years ago it was

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all pseudo-science, it was
all made up. No one had the

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vaguest idea what genes
were present in people's DNA.

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They didn't even know about DNA.
They didn't really know about most

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Mendelian traits being
passed in human populations.

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And they had no way of knowing,
in the vast majority of cases,

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whether a certain person's phenotype
was or was not dictated by genotype.

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So is this notion of a strong
genotype-phenotype connection

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totally nonsense? Well,
I'll give you an example of

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where you might begin to think it
isn't. And it comes from studies of

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identical twins who were
separated at birth and brought up

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in different families. So
these identical twins obviously

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have an identical genotype.
So here's a famous story that I

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like to refer to. There
was a chance meeting in 1979

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between a steelworker named Jim
Lewis and a clerical worker named

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Jim Springer. They both lived
in Ohio. They were separated five

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weeks after birth and they were
raised 80 miles apart in different

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towns in Ohio. And
at the age of 39 they

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discovered themselves
through some change meeting.

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They discovered each other.
Well, they both had dark hair,

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they both stool six feet tall
and they both weighed 180 pounds.

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That's not so surprising. They both
spoke with the same inflections,

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which they clearly had not yet
learned to speak with when they were

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five weeks old. They
walked with the same gait.

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They made the same gestures.
They both loved stockcar racing.

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They both hated baseball. They
both married women named Linda.

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They were both divorced and in
their second marriages both of them

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married women named Betty.
They both drove Chevrolets.

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They drank Miller Lite. They
both chain smoked Salems.

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They vacationed on the same
half-mile of beach in Florida.

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They both had elevated blood
pressure, severe migraines,

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both had undergone vasectomies,
they both bit their nails, and their

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heart rates, their brainwaves and
their IQs were so similar that you

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couldn't tell whether it was the
same person or two separate people

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being studied. Now, what
do you begin to think of

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all that? Well,
that's an extreme case.

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The fact is most identical twins
raised apart do have a bit of

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divergence in their phenotype,
in the way they grow up, but it

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begins to plant in your mind the
notion that maybe many aspects of

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the way we think and act actually
have a strong genetic template in

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them. And one can begin to study
identical twins and ask things about,

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especially those who are separated
at birth, and not use such extreme

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anecdotes like the one I just used.
And one begins to find that there's

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an impressive list of attributes
that can only be explained by their

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being a strong genetic determinant
in them. And these traits include

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being alienated by people around one,
extroverted, being a traditionalist,

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looking backwards in terms
of one's customs, leadership,

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career choice, risk aversion,
attention deficit disorder,

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religious conviction and
vulnerability to stress.

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Heritability it turns out,
if you study identical twins,

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is about, I'm sorry, happiness,
if you study identical twins, is

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about 80% heritable it turns out
and depends little on one's wealth,

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achievement or marital status. But
80% of it, if you study identical

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twins, seems to have a genetic
template. And you'll say,

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well, that's all very satisfying,
but it begins to be a little

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unsettling because it begins to
cause each of us to ask are we

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really who we think we are or are we
just kind of cassette recorders who

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are playing out the program that was
stuffed into us when the sperm hit

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the egg that lead to each
of our appearing on the face

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of the planet? To what
extent are we individuals or

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to what extent are we simply
manifestations of genotype?

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And to what extent do we have
freewill? That's kind of an

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interesting question.
Now, people like Eric,

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I'm not pointing an accusing finger,
people like Eric have begun to

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refine the science of genetics
so it really is a science.

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And so, restriction
fragment polymorphisms,

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SNPs, haplotype analysis are now
uncovering a staggering array of

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human traits. I believe that the
number of human traits that have now

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been localized, specific
genes, most of these are

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diseased genes, exceeds
2,000 is my recollection.

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And there are only 21,000,
22,000 genes in the human genome.

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And the pace with which genes
and genotype and phenotype will be

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linked to one another is going
to increase if nothing else.

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Many of the traits that one thinks
about in terms of human beings are

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obviously polygenic. They're
not single strong Mendelian

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alleles with strong penitence.
They represent the confluence,

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the collaboration of multiple
alleles that are conspiring to

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create one or another phenotype.
And these polygenic traits or even

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polygenic diseases have
traditionally resisted analysis

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because mathematically they
are so complex to dissect out,

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to dissect out the contributing
genes which together as a cohort

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create a genotype. But,
as Eric told you last time,

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people like you who are great
software developers will one day

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begin to figure out how one can take
extraordinarily complex datasets and

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begin to associate specific
chromosomal regions,

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and ultimately genes, with
specific genetic sequences that

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contribute to a polygenic trait.
I think at one time Eric spent,

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about three or four years ago,
he worked with people at Cornell

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studying the polygenic trade
of ripening in tomatoes.

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It's a polygenic trait like
probably chess playing ability in

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human beings. And was able to
localize ripening rate of tomatoes

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to five or six distinct genetic
regions in the chromosomes of the

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tomato plant. But that's only
a harbinger of what could come.

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So let's imagine now, again,
I'm not blaming Eric for this,

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I'm just telling you he's the one,
he more than anyone else almost on

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the planet is the person who is
leading the charge to refine and

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strengthen these extraordinarily
powerful tools that enable us to

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discern how our genome
creates us the way we are.

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But he's not going to be the
one who applies these tools.

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They'll be applied
all over the planet.

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There are geneticists everywhere
who are interested in looking at how

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different aspects of human phenotype,
including disease phenotype are

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governed by the alleles, by
the SNPs, by the polymorphisms

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that we carry, and
obviously by the genes and

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proteins that we make.
So let's begin to imagine,

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let's put ourselves fast-forward
ten years and begin to imagine where

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this is going to take us.
We already know about a very

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substantial number of genes that
determine the risk of different

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kinds of cancer, i.e.,
there's at least 15 different

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cancer syndromes that people have
which have been associated with

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specific genetic loci. I
talked briefly about retinal

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blastoma, which is a rare one,
but even commonly occurring cancers

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will soon be connected with
specific alleles in the genome.

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And the risk of getting them in
one's lifetime will be relatively

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accurately predictable. It
might take another decade but it

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will happen. Manic depressiveness,

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some people have great swings in
mood. 2% or 3% of the population

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doesn't wake up happy every morning.
And this is also, I believe, going

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to yield two specific analyses
and association with certain genes.

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There's already a suggestion
that the D4 dopamine receptor,

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which is involved in receiving
one of the neurotransmitters in the

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brain, may have a polymorphism
that's connected with manic

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depressiveness. There will
be probably alleles which

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are connected with, in some
way, novelty or adventure

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seeking. There are going to be
alleles that are associated with

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00:19:37,000 --> 00:19:41,000
anxiety, probably maybe connected
with the serotonin transporter in

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00:19:41,000 --> 00:19:45,000
the brain. Cardiac disease
susceptibility is already mapped out

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00:19:45,000 --> 00:19:49,000
in a number of traits in
the most extreme cases,

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00:19:49,000 --> 00:19:53,000
but cardiac disease is very
frequent in this population.

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And there undoubtedly will be
alleles that are discovered that

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determine whether one has a high
risk or low risk of getting heart

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00:20:01,000 --> 00:20:05,000
disease, of getting arthrosclerosis,
and whether or not one can go to

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McDonald's every day and
Big Macs with impunity.

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00:20:10,000 --> 00:20:13,000
Can one do that or not?
Some people probably can.

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00:20:13,000 --> 00:20:17,000
Some people can eat as much salt as
they want and it doesn't give them

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high blood pressure.
Other people cannot.

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00:20:20,000 --> 00:20:24,000
We still don't really understand
that. Schizophrenia is probably

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00:20:24,000 --> 00:20:27,000
also very strongly genetically
templated, not totally but very

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00:20:27,000 --> 00:20:31,000
strongly. Susceptibility to
rheumatoid arthritis probably also

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00:20:31,000 --> 00:20:35,000
has a strong genetic component.
Difficulty or ease with which you

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solve math problems probably also
will one day be associated with a

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00:20:39,000 --> 00:20:43,000
certain number of genetic loci.
How many difficulties in learning

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00:20:43,000 --> 00:20:47,000
languages? There's already a trait
that was discovered in a family in

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00:20:47,000 --> 00:20:51,000
the Netherlands, I
believe, and they had a very

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00:20:51,000 --> 00:20:55,000
specific grammatical defect in the
way that they assembled the syntax

303
00:20:55,000 --> 00:20:59,000
of sentences associated with a
certain allele of a certain gene.

304
00:20:59,000 --> 00:21:03,000
Difficulty in just adding rows of
numbers may also be associated with

305
00:21:03,000 --> 00:21:07,000
certain combinations of alleles.
Now, you will say, well, it's

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00:21:07,000 --> 00:21:11,000
impossible, it's inconceivable that
these different aspects of cognitive

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00:21:11,000 --> 00:21:15,000
function can be associated
with a small number of genes.

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00:21:15,000 --> 00:21:19,000
But let me tell you something
else. We talked a week ago about the

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00:21:19,000 --> 00:21:24,000
evolution of humanity over the
last couple hundred thousand years.

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And the pace with which the human
brain has evolved over the last half

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00:21:28,000 --> 00:21:32,000
million years, and more
recently the last 200,

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00:21:32,000 --> 00:21:37,000
00 years, has been so frighteningly
rapid that the evolution of

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00:21:37,000 --> 00:21:41,000
cognitive function and perception
in different ways can only have

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00:21:41,000 --> 00:21:46,000
happened through the actions
of a small number of genes.

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00:21:46,000 --> 00:21:50,000
If one needed to have dozens of
genes change in concert in order to

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00:21:50,000 --> 00:21:55,000
acquire the penetrating minds that
we now have in which our ancestors

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00:21:55,000 --> 00:21:59,000
500,000 years didn't have,
the evolution could not have

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00:21:59,000 --> 00:22:04,000
occurred so quickly. And,
for that reason alone,

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00:22:04,000 --> 00:22:08,000
one begins to suspect that the
genetic differences between people

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00:22:08,000 --> 00:22:13,000
who lived 500, 00
years ago visa vie their

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00:22:13,000 --> 00:22:18,000
cognitive function and
ours are not so large. And,

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00:22:18,000 --> 00:22:22,000
therefore, a rather small number of
genes may have been responsible for

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00:22:22,000 --> 00:22:27,000
conferring on us the powerful minds
which we now, which most of us,

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00:22:27,000 --> 00:22:32,000
I didn't say anything,
which most of us now possess.

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So where is this going to take us?
What are the consequences of this?

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00:22:36,000 --> 00:22:41,000
Let's imagine ten or twenty years
down the road when we can do some

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00:22:41,000 --> 00:22:46,000
kind of SNP analysis on one of these
chips that have been developed in

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00:22:46,000 --> 00:22:50,000
California and here and in various
places. And we can begin to imagine

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00:22:50,000 --> 00:22:55,000
the allelic diversity in a newborn
child's DNA or even prenatally

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if you want. So what are
you going to do if you

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00:23:00,000 --> 00:23:04,000
begin to find on a chip of a child's
DNA that this kid is likely to be

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00:23:04,000 --> 00:23:08,000
very good in language, probably
is going to have poor math

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00:23:08,000 --> 00:23:12,000
skills, will be a rather
anxious and obsessive person,

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00:23:12,000 --> 00:23:17,000
will have difficulty associating
with his or her peers,

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00:23:17,000 --> 00:23:21,000
and is likely to come down with
heart disease at the age of 45?

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00:23:21,000 --> 00:23:25,000
How is that going to affect
your relationship to that

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00:23:25,000 --> 00:23:29,000
person, that child? And
will you give that child a

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00:23:29,000 --> 00:23:33,000
different kind of education than a
newborn who has SNPs which indicate

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00:23:33,000 --> 00:23:37,000
that without doubt they're going
to get 1600s on their morning boards

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and their shoe-ins for admission
to MIT? Are you going to treat those

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00:23:41,000 --> 00:23:44,000
kids the same or are you going
to treat them differently?

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Do you give them the same kind
of education and nurturing?

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And how do you treat them
throughout their elementary and high

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school? Are you going to segregate
them into different groups or is

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everybody going to be
given an equal chance?

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00:24:00,000 --> 00:24:04,000
Well, you might say it's our
tradition in this country to give

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everybody equal footing, in
part because of a reaction to

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what happened in World War II in
no small part. But what if the time

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comes when people say we need to be
more efficient economically in this

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00:24:17,000 --> 00:24:21,000
country and we need to devote our
resources, need to maximize the

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00:24:21,000 --> 00:24:26,000
investment, the benefit we
get from various investments,

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00:24:26,000 --> 00:24:30,000
and so it's much more efficient to
put kids in a certain genetic class

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in one school and kids who have
another level of genetic giftedness

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00:24:34,000 --> 00:24:38,000
in another school? Of
course much of this will be

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00:24:38,000 --> 00:24:42,000
foolhardy because all
of these genetic tests,

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00:24:42,000 --> 00:24:45,000
although they will give you
probabilities of certain phenotypes,

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00:24:45,000 --> 00:24:49,000
they'll never, at least for the
foreseeable generation or two give

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00:24:49,000 --> 00:24:52,000
you certainties. No one
will be able to predict with

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00:24:52,000 --> 00:24:56,000
absolute total certainty about the
potentials of one or another young

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00:24:56,000 --> 00:25:00,000
person on the basis of DNA tests,
at least not in the near future.

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00:25:00,000 --> 00:25:04,000
Right now one can predict with total
certainty that somebody who has a

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00:25:04,000 --> 00:25:08,000
certain allele will come down with
Huntington's disease at the age of

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00:25:08,000 --> 00:25:12,000
30 or 40 or 50. There
the predictability,

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00:25:12,000 --> 00:25:16,000
the penitence is 100%. But what
if somebody has an allele that says

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00:25:16,000 --> 00:25:20,000
with 60% likelihood they're
not going to very good at math?

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00:25:20,000 --> 00:25:24,000
Is that already going to be enough
to justify their segregation amongst

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00:25:24,000 --> 00:25:29,000
a group of the
mathematically less gifted?

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00:25:29,000 --> 00:25:33,000
Let's say that they've gone through
elementary and secondary education

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and high school and they've made
it through college and they start

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looking for employment.
Actually, there are jobs out here

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00:25:41,000 --> 00:25:45,000
to be had in this economy,
you wouldn't know it, but there

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actually are people who can find
jobs. And let's say one has now an

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00:25:49,000 --> 00:25:53,000
employer who is evaluating a certain
job candidate for employability.

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00:25:53,000 --> 00:25:57,000
Maybe they'd like to have a good
medical checkup before they employ

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00:25:57,000 --> 00:26:01,000
this person ostensively to see
whether this person is healthy

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00:26:01,000 --> 00:26:05,000
enough to last for ten or twenty
or thirty years of employment.

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00:26:05,000 --> 00:26:09,000
And maybe they'd like to include
among that medical exam that

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00:26:09,000 --> 00:26:13,000
person's DNA just in case.
And what if the DNA tells the

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00:26:13,000 --> 00:26:17,000
employer that this individual is
likely to get colon cancer in 18

380
00:26:17,000 --> 00:26:21,000
years and has a slight
susceptibility to mood instability

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00:26:21,000 --> 00:26:25,000
and perhaps even
manic depressiveness,

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00:26:25,000 --> 00:26:29,000
that this person is not one of those
who can go to McDonald's and eat Big

383
00:26:29,000 --> 00:26:34,000
Macs with impunity but has a
tendency to arthrosclerosis?

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00:26:34,000 --> 00:26:37,000
You can think of whatever
possibilities you will.

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00:26:37,000 --> 00:26:41,000
Will that be, therefore, a
ground to reject that person as an

386
00:26:41,000 --> 00:26:45,000
employee? Well, you'll say
they really have no right

387
00:26:45,000 --> 00:26:49,000
to do that. But keep in mind that
with increasing frequency in this

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00:26:49,000 --> 00:26:53,000
society medical benefits,
medical insurance is paid by the

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00:26:53,000 --> 00:26:57,000
employer. So does the employer want
to have a whole workforce of people

390
00:26:57,000 --> 00:27:01,000
who are in various stages of
terminal disease or would this

391
00:27:01,000 --> 00:27:05,000
employer like to be able to pay
the lowest possible health benefits

392
00:27:05,000 --> 00:27:09,000
because the employer has taken care
to employ only people who have a

393
00:27:09,000 --> 00:27:13,000
really terrific genotype,
whatever that is defined as being

394
00:27:13,000 --> 00:27:17,000
arbitrarily admittedly? And
what about marriagability?

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00:27:17,000 --> 00:27:21,000
As my sister always says to me, if
you want to marry a man the first

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00:27:21,000 --> 00:27:25,000
thing you should do is look
into his genes. That's a double

397
00:27:25,000 --> 00:27:34,000
entendre. Anyhow.

398
00:27:34,000 --> 00:27:35,000
See, somebody finally
got it. [LAUGHTER]

399
00:27:35,000 --> 00:27:44,000
The fact is that
maybe certain

400
00:27:44,000 --> 00:27:49,000
people will be deemed to be
less desirable genetically.

401
00:27:49,000 --> 00:27:54,000
Well, the fact is we've been doing
that for the last million years.

402
00:27:54,000 --> 00:27:59,000
If you're attracted to someone and
you end up marrying them then they

403
00:27:59,000 --> 00:28:04,000
have phenotypes which you think
are in one way or another valuable.

404
00:28:04,000 --> 00:28:08,000
Consciously or unconsciously,
you are practicing a form of

405
00:28:08,000 --> 00:28:12,000
eugenics. But obviously there
could be a much more subtle form of

406
00:28:12,000 --> 00:28:16,000
eugenics where part of the marriage
contract states that you want a

407
00:28:16,000 --> 00:28:20,000
sample of that person's buccal swab
or some lymphocytes to check out

408
00:28:20,000 --> 00:28:24,000
what kind of DNA he or she has.
Now you say, well, that could never

409
00:28:24,000 --> 00:28:29,000
happen. But it happens
today regularly.

410
00:28:29,000 --> 00:28:32,000
There are villages in Greece where
there are a substantial percentage

411
00:28:32,000 --> 00:28:36,000
of people who carry the trait
sickle cell anemia which,

412
00:28:36,000 --> 00:28:40,000
as you may know, is not so serious
phenotypically in heterozygous form,

413
00:28:40,000 --> 00:28:44,000
but in the homozygous form
is actually devastating.

414
00:28:44,000 --> 00:28:47,000
And the reason they have sickle
cell anemia is that those areas of

415
00:28:47,000 --> 00:28:51,000
Greece historically had
high rates of malaria. And,

416
00:28:51,000 --> 00:28:55,000
as you may know, sickle cell
anemia actually protects,

417
00:28:55,000 --> 00:28:59,000
in the heterozygous state actually
protects one from the ravages of the

418
00:28:59,000 --> 00:29:03,000
malarial parasite. So
about 20 years ago it became

419
00:29:03,000 --> 00:29:07,000
possible to do a simple genetic test
to determine whether an individual

420
00:29:07,000 --> 00:29:11,000
was heterozygous for sickle cell
anemia. And what happened is that

421
00:29:11,000 --> 00:29:15,000
somehow what was supposed to be
confidential medical genetic tests

422
00:29:15,000 --> 00:29:19,000
got out. They became public.
And young individuals in the

423
00:29:19,000 --> 00:29:23,000
population became known as carrier,
as heterozygotes for sickle cell

424
00:29:23,000 --> 00:29:27,000
trait, even though phenotypically
they were reasonably normal because

425
00:29:27,000 --> 00:29:32,000
the heterozygote condition
is not so devastating.

426
00:29:32,000 --> 00:29:36,000
So those individuals were soon
ostracized, to use an old Greek word.

427
00:29:36,000 --> 00:29:40,000
They were soon put to the side.
They were placed in the pool of the

428
00:29:40,000 --> 00:29:44,000
unmarriable because nobody wanted
to marry them. And so they then,

429
00:29:44,000 --> 00:29:49,000
as a consequence, began to
marry amongst themselves.

430
00:29:49,000 --> 00:29:53,000
Remember what I told you about
homozygosis with the sickle cell

431
00:29:53,000 --> 00:29:58,000
trait. But that's only
one example of that.

432
00:29:58,000 --> 00:30:01,000
Among Orthodox Jews, among
Ashkenazi Jews between 2% and

433
00:30:01,000 --> 00:30:05,000
3% of the population carries an
allele for Tay-Sachs disease which

434
00:30:05,000 --> 00:30:09,000
is phenotypically silent in the
heterozygous state but in the

435
00:30:09,000 --> 00:30:13,000
homozygous state is a devastating
condition which leads to death in

436
00:30:13,000 --> 00:30:17,000
the first years of life. So
now among the Orthodox Jews in

437
00:30:17,000 --> 00:30:21,000
New York before two young people
will get married they will do a test

438
00:30:21,000 --> 00:30:25,000
to see whether they are
heterozygous for the Ta Sacks allele.

439
00:30:25,000 --> 00:30:29,000
And, in fact, it's not limited
any longer to Orthodox Jews.

440
00:30:29,000 --> 00:30:32,000
Because if they're both
heterozygotes their marriage to one

441
00:30:32,000 --> 00:30:36,000
another, in spite of
anything else they consider,

442
00:30:36,000 --> 00:30:40,000
is strongly discouraged. Among
those who don't live in such

443
00:30:40,000 --> 00:30:43,000
a closely structured society such
people might nonetheless decide to

444
00:30:43,000 --> 00:30:47,000
get married and then face the
devastating possibility of one of

445
00:30:47,000 --> 00:30:51,000
their four offspring on average
coming out as a homozygote and

446
00:30:51,000 --> 00:30:55,000
having an incurable genetic
disease which is going to lead

447
00:30:55,000 --> 00:30:59,000
to their early death. But
what about other traits?

448
00:30:59,000 --> 00:31:03,000
And what time will this
genetic discrimination,

449
00:31:03,000 --> 00:31:07,000
where will it begin and where
will it end? What if you find an

450
00:31:07,000 --> 00:31:12,000
individual who has a trait of manic
depressiveness among relatives?

451
00:31:12,000 --> 00:31:16,000
And when will these
genetic tests become public?

452
00:31:16,000 --> 00:31:20,000
When will they be private
knowledge? You say, well,

453
00:31:20,000 --> 00:31:25,000
they can all be kept private.
But ultimately there are already

454
00:31:25,000 --> 00:31:29,000
insurance companies which are
demanding to determine whether and

455
00:31:29,000 --> 00:31:33,000
individual can be insured by looking
at whether they have genes for

456
00:31:33,000 --> 00:31:38,000
certain kinds of
disease-causing alleles.

457
00:31:38,000 --> 00:31:42,000
After all, why should they insure
somebody, give somebody life

458
00:31:42,000 --> 00:31:46,000
insurance if they are likely to come
down with Huntington's disease at

459
00:31:46,000 --> 00:31:50,000
the age between 35 and 40,
which will surely and inevitably

460
00:31:50,000 --> 00:31:54,000
lead them to an early grave?
You'll say, well, we cannot have

461
00:31:54,000 --> 00:31:58,000
genetic information like that become
public or even become accessible.

462
00:31:58,000 --> 00:32:02,000
Maybe that's a solution. The
problem is we've been talking

463
00:32:02,000 --> 00:32:06,000
about these issues for 10
to 15 years in this society,

464
00:32:06,000 --> 00:32:10,000
and we've not yet converged any kind
of solution. And the solutions to

465
00:32:10,000 --> 00:32:14,000
these problems should not be left
in the hands of molecular biologists,

466
00:32:14,000 --> 00:32:18,000
because molecular biologists or
biologically cognizant people by now,

467
00:32:18,000 --> 00:32:23,000
like you, are no more gifted and no
more insightful to deal with these

468
00:32:23,000 --> 00:32:27,000
issues than anyone else is.
They're intuitively obvious these

469
00:32:27,000 --> 00:32:31,000
issues. You don't need to know
about SNPs to begin to understand

470
00:32:31,000 --> 00:32:35,000
the potentially devastating impacts
that the misuse of genetics can have

471
00:32:35,000 --> 00:32:40,000
on our society. And what
happens if one of these

472
00:32:40,000 --> 00:32:44,000
days people discover alleles
for certain aspects of cognitive

473
00:32:44,000 --> 00:32:48,000
function? Chess playing ability.
The ability to learn five different

474
00:32:48,000 --> 00:32:52,000
languages. The ability to
remember strings of numbers.

475
00:32:52,000 --> 00:32:56,000
The ability to speak
extemporaneously in front of a class,

476
00:32:56,000 --> 00:33:00,000
for what it's worth, for 50
minutes several times a week.

477
00:33:00,000 --> 00:33:05,000
Whatever
ability you want,

478
00:33:05,000 --> 00:33:09,000
valued or not so valued, what if
those alleles begin to come out?

479
00:33:09,000 --> 00:33:14,000
And here's the worse part. What
if somebody begins to look for the

480
00:33:14,000 --> 00:33:18,000
frequency of those alleles in
different ethnic groups scattered

481
00:33:18,000 --> 00:33:22,000
across this planet?
Now, you will say to me,

482
00:33:22,000 --> 00:33:27,000
well, God has made all his children
equal. But the fact is if you look

483
00:33:27,000 --> 00:33:31,000
at the details of human evolution,
some of which I discussed with you a

484
00:33:31,000 --> 00:33:36,000
week ago, last week, you'll
come to realize that most

485
00:33:36,000 --> 00:33:40,000
populations in humanity are
the modern descendents of very

486
00:33:40,000 --> 00:33:45,000
small founder groups. Remember
about the story of the Fins.

487
00:33:45,000 --> 00:33:50,000
70% of Finish men carry the same
Y chromosome. All modern Fins,

488
00:33:50,000 --> 00:33:55,000
most modern Fins, all of them are
likely to be the descendents of a

489
00:33:55,000 --> 00:34:00,000
small founder group that
came into Finland 2,000 or 3,

490
00:34:00,000 --> 00:34:05,000
00 years ago and carry with them the
peculiar set of polymorphisms that

491
00:34:05,000 --> 00:34:09,000
founder group happens to have had.
And arguments like that begin to

492
00:34:09,000 --> 00:34:13,000
persuade you that there'll be
different allele frequencies in

493
00:34:13,000 --> 00:34:17,000
different populations of humanity.
What if somebody begins to discover

494
00:34:17,000 --> 00:34:21,000
that Macedonians have an enormously
high rate of the ability to play

495
00:34:21,000 --> 00:34:25,000
chess because of a certain
allele? And here I'm talking very

496
00:34:25,000 --> 00:34:29,000
speculatively. I'm not
literally meaning that.

497
00:34:29,000 --> 00:34:33,000
And Tibetans have a very poor
ability to construct software

498
00:34:33,000 --> 00:34:38,000
programs because of a genetic allele
they carry? I hope nobody's Tibetan

499
00:34:38,000 --> 00:34:42,000
here. I tried to choose two.
Are there any Macedonians? All

500
00:34:42,000 --> 00:34:47,000
right. I succeeded. All
right. Anyhow. So the fact is

501
00:34:47,000 --> 00:34:51,000
it's inescapable that different
alleles are going to be present with

502
00:34:51,000 --> 00:34:56,000
different frequencies in different
inbreeding populations of humanity

503
00:34:56,000 --> 00:35:00,000
or populations of humanity that
traditionally have been genetically

504
00:35:00,000 --> 00:35:05,000
isolated from one another. It's
not as if all the genes that we

505
00:35:05,000 --> 00:35:09,000
carry have been mixed with everybody
else's genes freely over the last

506
00:35:09,000 --> 00:35:13,000
100,000 years. Different
groups have breed

507
00:35:13,000 --> 00:35:17,000
separately and have, for
reasons that I've told you,

508
00:35:17,000 --> 00:35:21,000
founder affects and genetic
drift acquired different sets and

509
00:35:21,000 --> 00:35:25,000
different constellations of alleles.
So what's going to happen then, I

510
00:35:25,000 --> 00:35:29,000
ask you without wishing to hear an
answer because nobody really knows?

511
00:35:29,000 --> 00:35:32,000
Then for the first time there could
be a racism which is based not on

512
00:35:32,000 --> 00:35:36,000
some kind of virulent ideology,
not based on some kind of kooky

513
00:35:36,000 --> 00:35:40,000
versions of genetics,
because the eugenicists in the

514
00:35:40,000 --> 00:35:43,000
beginning of the 20th century, as
well as the Nazis hadn't had any

515
00:35:43,000 --> 00:35:47,000
idea about genetics, they
were just using the word,

516
00:35:47,000 --> 00:35:51,000
even though they knew nothing
about the science of genetics as we

517
00:35:51,000 --> 00:35:55,000
understand it today. But
what happens if now for the

518
00:35:55,000 --> 00:35:58,000
first time we, i.e., you
who begin to understand

519
00:35:58,000 --> 00:36:02,000
genetics, begin to perceive
that there are, in fact,

520
00:36:02,000 --> 00:36:06,000
different populations of humanity
that are endowed with different

521
00:36:06,000 --> 00:36:10,000
constellation of alleles that we
imagine are more or less desirable?

522
00:36:10,000 --> 00:36:13,000
What's going to happen then? I
don't know. But some scientists

523
00:36:13,000 --> 00:36:17,000
say, well, the truth must come
out and that everything that can be

524
00:36:17,000 --> 00:36:21,000
learned should be learned, and
we will learn how to digest it

525
00:36:21,000 --> 00:36:25,000
and we will learn how to live with
that. But I'm not so sure that's

526
00:36:25,000 --> 00:36:29,000
the right thing. And you
all have to wrestle with

527
00:36:29,000 --> 00:36:32,000
that as well. And even
more insidious is the

528
00:36:32,000 --> 00:36:36,000
following notion. Remember
the story about the two

529
00:36:36,000 --> 00:36:40,000
Jims, the two guys from Ohio who met
one another at the age of 39 after

530
00:36:40,000 --> 00:36:44,000
they'd been separated at five
weeks of birth? That story begins to

531
00:36:44,000 --> 00:36:48,000
persuade you of something I said
before, and that is that a lot of

532
00:36:48,000 --> 00:36:52,000
what you think you are isn't
what you made of yourself,

533
00:36:52,000 --> 00:36:56,000
isn't what your parents made
of yourself, isn't what your

534
00:36:56,000 --> 00:37:00,000
environment made of you
and your experiences.

535
00:37:00,000 --> 00:37:04,000
Maybe it's all just in your genes.
And if that's so then maybe you

536
00:37:04,000 --> 00:37:08,000
can't take credit for any of
the good things you've done.

537
00:37:08,000 --> 00:37:12,000
And conversely maybe you're not
responsible for all the bad things

538
00:37:12,000 --> 00:37:16,000
you've done. Maybe three years from
now somebody will begin to plead

539
00:37:16,000 --> 00:37:20,000
that even though they were
not criminally insane when they

540
00:37:20,000 --> 00:37:24,000
committed a string of serial murders,
in fact it really wasn't their fault

541
00:37:24,000 --> 00:37:28,000
because they happen to have this
particular genotype which is known

542
00:37:28,000 --> 00:37:32,000
to be correlated with a
strong tendency to violent.

543
00:37:32,000 --> 00:37:35,000
And, by the way, there
is an allele which has a

544
00:37:35,000 --> 00:37:39,000
correlation, I forget which one it
is, has a correlation with violent

545
00:37:39,000 --> 00:37:43,000
behavior. So what if one begins to
write off everything we do as not a

546
00:37:43,000 --> 00:37:46,000
reflection of our own freewill,
our own volition, but instead a

547
00:37:46,000 --> 00:37:50,000
consequence of the genes which
our parents hoisted on us?

548
00:37:50,000 --> 00:37:54,000
Of course, we can blame it on them.
As a father of children, I can tell

549
00:37:54,000 --> 00:37:58,000
you that it's amazing how many
different things can be blamed on

550
00:37:58,000 --> 00:38:02,000
the parents. [LAUGHTER] Of
course, the parents have their

551
00:38:02,000 --> 00:38:06,000
own out. The parents can
blame it on their parents.

552
00:38:06,000 --> 00:38:10,000
So now it goes back to the
grandparents, back to the beginning

553
00:38:10,000 --> 00:38:14,000
of time. We laugh about these
things and they are amusing,

554
00:38:14,000 --> 00:38:18,000
but they are taking us on a
collision course with some very

555
00:38:18,000 --> 00:38:22,000
difficult problems. And you
guys have to wrestle with

556
00:38:22,000 --> 00:38:26,000
them and you guys have to explain
to the people who haven't taken 7.

557
00:38:26,000 --> 00:38:31,000
12 where the world of
biology is taking us.

558
00:38:31,000 --> 00:38:35,000
And on that note, I want
to tell you that Eric and I

559
00:38:35,000 --> 00:38:40,000
have enormously enjoyed
being with you this semester.

560
00:38:40,000 --> 00:38:44,000
We wish you much luck and
success in your future lives.

561
00:38:44,000 --> 00:38:49,000
We hope some of you have become
interested in biology and that you

562
00:38:49,000 --> 00:38:53,000
found this course a little different
from what you took in high school.

563
00:38:53,000 --> 00:38:58,000
And have a wonderful winter
vacation. See you. [APPLAUSE]