Volume 10, Issue No. 2
Cracking the Code of Life
About This Issue...
Basic Facts
Humans have one and a half times more
• Genes are the inherited recipes
for the proteins that build and
operate our bodies.
of them than a round worm, two times
• They are written in the language
of DNA, a code of four “letters”
(A, T, C, and G, representing four
chemicals).
• Genes are responsible for
specific traits like eye color
and height.
• Mutations are changes in the
DNA sequence of a gene.
• Mutated genes cause thousands
of genetic diseases that are
presently incurable.
• The genome is the entire set of
DNA on our 23 pairs of
chromosomes.
more than a fruit fly, and 300 different
from a mouse. What are they?*
For scientists, February 12, 2001, was like seeing
the Earth from outer space for the first time. It was
the day they saw the printout of the entire human
genome, a swirl of cluttered and disordered chromosomes teeming with elements from other species and
just a few scattered human genes. It was humbling.
“A person who gazes upon the human genome is
likely to walk away feeling a little bit less the center
of attention,” said one scientist.
The genome is so important that we
sometimes call it the “book of life,” and
scientists undertook a massive, international effort (the Human Genome Project)
to read its text. They expected to find at
least 100,000 genes because they thought the
human being is so complicated that it must
need that many genes to function. But to their
surprise they found only about 30,000
genes. Of the six feet of DNA coiled
inside every cell’s nucleus, only one inch
is devoted to genes - not much more
than in worms. And about 98% of our
genes are the same as they found in mice.
These surprising discoveries lead to more
questions: How do our genes function to
produce such a complex organism as the
human being?
Scientists used to think that one gene makes one
protein. But now they are discovering that human
genes can make up to ten different proteins by
*Answer: The number of genes in the human genome.
2 Cracking the Code of Life
reading different parts of the DNA code to compose
proteins. Further, proteins combine like Legos® to
make complex proteins that interact with others. So
even though we may not have many genes, we have
lots of proteins – up to 100,000 – and these are the
true basis of our biology.
Likewise, the human
genome is not just made up of
genes. Ninety-eight percent
of it is made of DNA that
doesn’t code for anything.
Scientists previously dismissed the non-gene DNA as
“junk.” We have more noncoding DNA in our genome
than in any other organism
that has been sequenced so
far. Now that we have the
human genome sequence, we
might be able to figure out
what this “junk” really does.
Clearly, we are not just
printouts of our genes.
Sequencing the human
genome was a great challenge
of the last century. Figuring
out how these genes make us
human is the adventure of
the next. In the following
articles, you will read about
the complicated landscape of
the genome and about what
genes can already tell us
about our health and our
abilities. You can also join in
the debate about the downside of having our genomes
become an “open book” for
all to see.
Contents...
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Three Books in One ................................................................. 4
Why Tay-Sachs Disease? ..........................................................6
The Breast Cancer Gene: Fate or Risk? ...................................... 8
Of Mice and Memory ........................................................... 10
Iceland: 1,100+ Years of Genetic Solitude ............................... 12
Profile: Bruce T. Lahn, Researching the Why of the Y .............. 14
Something you can try: Crack This Code! ............................... 15
Resources .............................................................................. 16
Dear Readers,
The Biotechnology Institute is pleased to present this issue of Your World
dedicated to explorations of the human genome, one of the most exciting
and provocative areas of biotechnology today. I am particularly delighted
that this issue coincides with the release of a television special titled
“Cracking the Code of Life” produced by NOVA/WGBH-TV and broadcast on
April 17, 2001. The Institute is pleased to have worked with NOVA/WGBH on
the editorial content of this issue of Your World, to provide teachers and
students a richer education package.
Sincerely,
Paul Hanle, President
Biotechnology & You
Volume 10, Issue No. 2
Published by:
Jeff Alan Davidson
In Partnership with:
Biotechnology Industry Organization (BIO)
Neo/SCI Corporation
Pennsylvania Biotechnology Association
Writing by:
The Writing Company,
Cathryn M. Delude and
Kenneth W. Mirvis, Ed.D.
Design by:
Snavely Associates, Ltd.
Illustrations by:
Neo/SCI
Inside a cell, the nucleus
contains 23 pairs of chromosomes, which are made up of
deoxyribonucleic acid, or DNA.
The sequence of four chemicals
called “bases” – adenine (A),
thymine (T), cytosine (C), and
guanine (G) – contain the
genetic information in DNA.
Science Advisor:
William Nierman, The Institute for
Genomic Research
For more information:
Jeff Alan Davidson, Publisher
1524 W. College Avenue, Suite 206
State College, PA 16801
800-796-5806
www.BiotechInstitute.org
The Biotechnology Institute (BI) is a
national non-profit entity based in
Washington, DC, and dedicated to
education and research about
biotechnology. Our mission is to
engage, excite, and educate people
about biotechnology’s potential to solve
human health and environmental
problems. Your World focuses on
biotechnology issues and brings scientific
discoveries to life for 7th to 12th grade
students. We publish issues on different
topics each fall and spring. Please contact
Jeff Alan Davidson, Publisher, for
information on subscriptions (individual,
teacher, or library sets). Some back issues
are available.
This issue of Your World reflects some of
the issues and stories presented in
NOVA’s Cracking The Code of Life
episode (www.pbs.org/nova/genome).
Copyright 2001, BI. All rights reserved.
On the cover: The human genome contains the genetic information that
makes us all human, but each of us has variations that make us different individuals.
The Biotechnology Institute would like to thank the Pennsylvania
Biotechnology Association, which originally developed Your World.
Your World
3
What kinds of knowledge
can we gain from
studying the genome?
Imagine that each
chromosome is a DNA
continent. Most of these
continents would be vast
deserts that camouflage a
few gene settlements.
The DNA desert landscape
has patterns of endless repetitive
sequences of mostly the
chemical bases As and Ts that
show up as dark bands on the
pictures of stained chromosomes (karyotypes). The outskirts of gene towns have mostly Cs
and Gs, which show up as light bands. Chromosome 19 is one of
the smallest continents, but it is a genomic “tropical rainforest”
with the most genetic density. It has copied whole sections of 16
other chromosomes – or have they borrowed from it? Elsewhere,
chunks of continents have broken off and drifted into others.
And, like people looking for a new life, genes have jumped from
chromosome to chromosome. Such relocations may have allowed
genes to redefine themselves and take on new functions.
But what are those functions? Some genes are like on-off
switches. They either cause a disease like Tay-Sachs or
they don’t. Other genes act like dimmer switches on
timers, shining in different degrees of intensity throughout
your life. They might give you a high risk of cancer at age
40 or an allergic reaction to a cat tonight. Whether they
are switched on depends in part on whether you expose
yourself to cancer-causing chemicals or to cats. Many
genes work in complex networks we still don’t understand but that probably underlie conditions like heart
disease, diabetes, and obesity. Some genes come in
4 Cracking the Code of Life
Are there genes for adventure? Strength? Risk taking?
different personality flavors that might, for instance, influence
your thirst for adventure or your response to stress. Would you
prefer to climb Mt. Everest or read books by the fireplace? Will
you panic at the SATs or stay calm? But you are ultimately in
control – and your environment and experience greatly influence
how these genes influence you. You could satisfy your thirst for
adventure by being an entrepreneur instead of an explorer. You
could reduce stress by taking one AP course instead of five. As
one scientist said, you can’t blame your whole life on your genes.
Variations in genes shed light on our collective pasts.
Some genes have changed over the course of human history
in response to infections. The mutation that causes sickle
cell anemia, for example, was written
into the genome of people
who lived in mosquitoinfested areas because a
Is there a “bookworm” gene?
single copy of it protected them from malaria. Early technological
advancements have also edited our genome. A mutation that
happened to help people digest the sugar (lactose) in milk as
adults became common in people who developed dairy farming.
(The “normal” condition was to drink milk only as breast-feeding
babies.) This lactose-tolerance gene is shared by cultures as
diverse as northern Europeans, the Bedouins of the Middle East,
and the Tutsi of Africa.
The human genome reveals the bonds we share with all
animals, such as a set of genes that controls the way an embryo
develops from head to toe. Because we have similar genes, our
knowledge about flies and mice helps us
Short Arm
understand our own biology.
The genome also stores old rusting genes,
such as a ghost town of more than 100
“olfactory genes” that once gave our
evolutionary ancestors a keen sense of
smell. As humans evolved, perhaps we
stopped using these genes because we
started depending more on vision and
analytical thinking.
Our genome houses a menagerie of non-human genes, including some from bacteria and viruses
that infected us millions of years
ago. We’ve banished most of these
intruders to fossil pits in the DNA desert,
but we’ve adopted some as our own.
Centromere
Each chromosome assumes
the “X” shape when it has
duplicated itself just
before the cell divides.
The centromere
divides the chromosome into a long
and short arm, and
the telomeres
keep the ends of
each arm from
fraying.
Long Arm
Medical Text
Footnotes
Many people hoped the Human Genome Project’s
identification of disease genes would lead to new
treatments and cures. The newest genomic readout
shows 40 newly identified genes involved in conditions
ranging from epilepsy to color blindness. The challenge
is to discover the normal function of disease genes –
and how they malfunction. To their surprise, scientists
found 286 shadowy twins that duplicate
known disease genes, often on far-flung
chromosomes. These twins may
explain the mysteries about how
genetic diseases can behave so
differently in different people. Scientists are also pinpointing one-letter
variations (nicknamed SNPs) that
affect the way we respond to
medical drugs: a drug that helps
me might harm you because we
have a different SNP. This information will help doctors replace the current
“one-size-fits-all” drug therapy with a
more customized method.
For example, we use more than 100 bacterial genes to detoxify
poisons and regulate the brain chemistry that affects our moods.
Our genetic deserts are teeming with DNA parasites that seem
to have no purpose other than to reproduce and insert themselves
back into our DNA, making them the most common feature in
our genome. These parasites (called transposons or “selfish
DNA”) come in several varieties. One has parasites of its own
(called Alu elements). These tiny Alus account for 14% of the
entire genome: seven times the percentage of genes. They inhabit
the outskirts of the gene towns – and they only exist in humans
and primates – so they probably play a critical role in fine-tuning
our genes. One theory is that they adjust the dimmer switches on
some genes in response to stress.
All our genes interact with each other in ways so complicated
that our book of life reads like a tangled tale. Now, scientists are
untangling that tale into three versions: a shop manual on
human biology with a gene parts list; a history book with stories
of our evolutionary past; and a medical text book that helps us
conquer disease.
Career Connection: Evolutionary
Biologist: Study how our evolutionary past has shaped
human biology.
Telomere
Your World
5
Why do genes cause
genetic diseases?
Tay-Sachs disease is a parent’s nightmare. Your
beautiful, bouncing, healthy, happy baby gradually
can no longer hold his head up, see, move, or eat.
His nervous system degenerates, and he will die by
the age of five. There is nothing you can do.
The tragedy of Tay-Sachs begins when a child receives a
copy of a faulty gene from each parent. Each of these parents
carries one faulty copy, but they each have a normal version
that keeps them healthy. Each of their children then has a
25% chance of inheriting the deadly double dose, according to
the typical recessive inheritance pattern. Also, each child has
a 50% chance of inheriting one faulty gene and thus becoming
a carrier for a future generation.
Why would there be such a disease?
Genes don’t exist to cause
disease. They perform functions in
the body. If they become mutated,
they sometimes can’t perform their
normal function. That’s the case with Tay-Sachs. Normally,
the healthy Tay-Sachs gene produces part of an enzyme.
(An enzyme is a protein that reacts with and reorganizes
other molecules.) This particular enzyme, called HexA
Healthy Neuron
Lysosome (waste disposal site)
Neuron Affected by Tay-Sachs
Lipids (GM2 ganglioside)
Bulging Lysosome
(lipid waste accumulation)
6 Cracking the Code of Life
In healthy neurons, lysosomes
contain enzymes that break
down wastes from the cell. In
Tay-Sachs, one of those
enzymes (HexA) is inactive, so
waste lipids build up and
eventually destroy the neuron.
a four
is
(b-hexosaminidase A), breaks down
How do recessive
ow
achs
S
y
see h
a
o
T
t
other molecules. It works inside
diseases
start?
n
i
5
age 1
ation
p
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h
the cell’s waste disposal center,
Mutations
happen all the
o
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t
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affec
o
n
c
a
which is called the lysosome.
time
by
chance,
but only
t
c
os
es
yt
The m sertion. Tr and chang
Imagine a recycling center
some survive from generation
in
s,
where different workers are
to generation – depending on
letter s, deletion
n
o
i
.
assigned specific jobs for recycling
environmental
or social condit
e
r
n
inse
f a ge
o
”
different types of waste, such as
tions.
A
genetic
disease
starts
with
one
person. Imagine
g
n
i
“mean
glass, aluminum, or paper. In the
a baby girl born with a random mutation. If she survives,
same way, the lysosome has specialeach of her children could inherit a copy of that mutation.
ized disposal enzymes assigned to
The more children, the more potential copies. If the children
different waste molecules. In this case, HexA
belong to a group that is isolated or marries only within itself for
breaks down a lipid (fatty substance) called GM2 ganglioside.
religious or social reasons, the mutation will become common in
This lipid is used in the cells of the brain and nervous system, so
that population. Soon carriers of the mutation will have children
that’s where HexA is needed.
with double copies of it … and a recessive disease is born.
In Tay-Sachs, the gene for the HexA enzyme is
Scientists call this pattern the “founder effect” because only a few
mutated, so the enzyme can’t degrade the
people start (“found”) the disease in their descendents. (We’ll see
lipid. It’s as if the worker assigned to
another founder effect in the article on Iceland.)
glass stops working, so glass builds up
This pattern explains why Tay-Sachs is common
in the warehouse. The lipids build up
among Ashkenazi Jews, who make up 80% of modern
about it
in the lysosome, and the bulging
Jews. (One in twenty-seven Ashkenazi Jews carry one
lysosomes damage the cell. The nerve
copy of the Tay-Sachs gene.) Ashkenazi Jews moved
cells degenerate and die.
from Russia to Europe to escape persecution in the
Would you use such a
1600s. In Europe, they were confined to crowded urban
matchmaker service?
ghettos for centuries. They formed a tight-knit group
Would you still marry your
and didn’t marry outsiders, so there was a greater chance
true love if you both
What Should
that two people with a Tay-Sachs gene would marry. In
shared a Tay-Sachs gene?
that way, the Tay-Sachs gene became concentrated.
Be Done?
Furthermore, tuberculosis (TB), an extremely
Would other less-deadly
Genetic tests have really reduced the
infectious
and deadly disease, ran through the ghetto
genes affect your decision
number of Tay-Sachs babies born in
like
a
wildfire.
It reduced the population and further
to marry?
high-risk populations. If both you and
concentrated the Tay-Sachs gene. Some scientists even
wonder whether the carriers (with just one Tay-Sachs
your spouse are Tay-Sachs carriers,
gene)
were
somehow protected from TB. If so, people with the
you can choose to not have children or to have prenatal
normal gene would die while the carriers survived, making the
testing for the fetus. But what then? Should prenatal
Tay-Sachs gene even more common among descendents.
testing be required? Tay-Sachs also exists in the general
population, even though it is rare. Should genetic
What can be done?
testing be for just high-risk groups or for everybody?
For now, there is nothing that parents can do for a baby with
Tay-Sachs. Doctors cannot give babies a dose of the missing
Orthodox Jews don’t believe in prenatal testing, birth
enzyme because the brain, which is the organ most damaged by
control, or abortion. Still, they want to spare their
the disease, has a protective barrier that would keep the enzymes
community from the tragedy of
out. But genomic research may someday help. Scientists might
Tay-Sachs. They created a
modify a specific bacterium that infects the brains. They might
voluntary program of anonydisable it so it can’t cause disease and have it carry the gene for
mously registering people’s
HexA to the brain. Or they might transplant neurons with the
healthy gene in the brain to replace the damaged cells. They
DNA with a “matchmaker”
might devise drugs that prevent brain cells from making so many
who stores information about
lipids, so the enzyme has less work to do.
whether they carry the recessive disease gene. When
Career Connection: Disease Researcher:
they’re ready to marry, they
Use genomics to understand how diseases like diabetes
can ask the matchmaker if they
and asthma develop and how to control them.
and their “intended” share the
Tay-Sachs genes.
Think
!
Your World
7
How does a cell prevent
itself from growing out
of control?
DNA Mistakes and Damage
When Rachel’s high school biology class learned
about inherited diseases, it was a lesson that life
To understand the importance of this repair and maintenance function, let’s take a look at cell division. Cells are
supposed to make exact copies of the DNA in their chromosomes when they divide. But there is so much DNA to
duplicate that sometimes a cell makes a mistake. It may
substitute an A for a G, thus changing the amino acid that is
added to the protein chain. It may delete a whole section,
dropping amino acids from the protein. Or it may re-copy a
section, adding amino acids. The odds of this happening
when a single cell divides are small. But there are so many
cells in the body and they divide so many times over a lifetime
that it’s bound to happen somewhere, sometime.
had already taught her. Her mother had inherited a
“breast cancer gene,” and Rachel might have it,
too. That knowledge created nothing but uncertainty in their lives.
Rachel’s grandmother died of breast cancer when her mother
was only 10 years old, and her aunt survived breast cancer in her
30s but died of ovarian cancer in her 50s. Most breast cancer
does not run in families. But five percent of the overall cases are
linked to two mutant genes called BRCA1 and BRCA2. Rachel’s
mother got tested and found that she had a BRCA1 mutation.
This mutation does not guarantee that she will get breast cancer,
but it raises her risk of getting it – as well as ovarian cancer. (The
BRCA genes also raise the risk of cancers in men.)
When this mutation was linked to breast cancer, people
hoped it might lead to a cure, but so far it hasn’t. Scientists
are still figuring out what the normal functions of the
BRCA genes are and what happens when they
malfunction. The genes are both uncommonly
large and they produce huge proteins: 1,863
amino acids in the BRCA1 chain and 3,418 amino
acids in BRCA2. The normal versions of both proteins
interact with the molecules of a complex relay system for
repairing DNA damage and maintaining orderly cell division.
8 Cracking the Code of Life
What About Testing?
If there are no treatments, is genetic testing a good
idea? Women who test positive for BRCA1 (meaning
they have the mutation) suffer long-term stress, which
causes its own health problems. Life insurance companies worry that women will keep positive test results
secret and load up on insurance, but studies
show that few women do so. Some tests
only pick up common mutations; you
wouldn’t find out if you had an uncommon mutation for that disease.
Soon there will be tests for
many genetic conditions –
often with no treatments.
Then, all the kids in Rachel’s
class may have to
deal with uncertainties of knowing
their genes.
Repair and Checkpoints
Another
importan
t DNA re
called p5
pair gene
3, is mut
,
a
ted in th
cancer t
e majorit
umors.
y of
The chance of DNA damage is so great
that cells come equipped with a maintenance kit that repairs DNA and stops
damaged cells from dividing. The
BRCA1 gene is probably part of that kit. Its
protein may inspect the duplicated chromosomes before the cells divide. If there is a mistake, it
may signal other genes to repair it. If the repair fails, it
may signal another gene to stop the cell division or perhaps even
order the cell to “commit suicide.” If so, the BRCA1 gene plays a
part in the genome’s watchdog network for keeping cell division
under control.
When part of the repair kit itself is defective, though, a cell
with damaged DNA can still divide. That cell may be the first cell
of a cancer. Nothing checks its growth, so it multiplies. The new
cells have lost the ability to keep the pace of cell division slow and
steady. They multiply much more rapidly than normal cells and
become a tumor.
Worse, these rapidly multiplying cells make more DNA
copy mistakes – and the
DNA repair molecules can’t
fix them because they are
damaged. Thus, the tumor cells
gather more mutations. Indeed,
tumors caused by BRCA1 mutations
have many additional mutations not found in the normal cells.
Often, these additional mutations are in other DNA checkpoint
genes. It’s as if the guard stops guarding, so nothing stops the
tumor.
One day, understanding exactly how the BRCA genes
function – and malfunction – may give scientists new targets
for treating and even preventing breast cancer. Ideally, that
breakthrough would also help scientists tackle other forms of
cancer, since many different kinds of tumors also have defective repair genes.
Career Connection: Genetic
Diagnostic Developer: Develop ways to detect the
different mutations associated with a disease.
Damaged DNA
passes BRCA1
checkpoint
Abnormal cells
divide rapidly
How Some Breast Cancers
Begin: The BRCA1 mutation
fails to prevent a cell with a
new DNA defect from
dividing. The daughter cells
continue to divide, and new
mutations appear. The
abnormal cells divide rapidly
and form a tumor.
Your World
9
Photograph of mouse provided by Joe Tsien
Do genes play a role
in learning and
memory?
While Joe Tsien toiled away in graduate school and
beyond, he hoped to make a mark in the science of
bear directly on human learning, since we share the same
mechanisms. This understanding may one day lead to drugs
that can treat brain disorders or repair brains that have been
damaged by Alzheimer’s or stroke.
how we learn and remember. He never expected his
work to be the subject of a joke by David Letterman:
“Top Ten Term Paper Topics Written by Genius Mice.”
This Princeton University researcher had created smart mice
that he called “Doogies” after a boy genius on the TV show Doogie
Howser, MD. The Doogies had added genes that helped them
learn faster and remember more than regular mice. Almost
overnight, these mice became celebrities. A lot of people wondered if we would do that with humans, too.
Learning and Memory
Scientists had long proposed that a memory is produced when
two nerve cells act at the same time and strengthen the synapse
(gap) that allows information to flow from the first neuron to the
next. A certain receptor on the surface of the second neuron
opens up to receive the information that flows across the
synapse. (A receptor is a tiny pore that allows molecules to
enter the cell, and this one binds to a molecule called NMDA.)
NMDA receptors stay open longer in young animals than in
older ones, which might explain why young animals learn
faster and remember more. As young animals age, one part of
their NMDA receptor gets replaced with a component that doesn’t
stay open as long. To create smarter adults (Doogies), Joe Tsien
boosted the function of their NMDA receptors. He added an
extra copy of the longer-opening, young-mouse component. The
Doogies’ receptors stayed open twice as long as those in normal
adults, and they made synapse connections that were as strong
as those in young mice. But how would they do on the test? A
mini-Educational Testing Service quiz showed that the Doogie
mice remembered new objects three times longer than normal
adult mice, and they also learned faster and formed better
analytical strategies in negotiating a water maze.
These results confirmed the prediction that stronger
synapses mean faster learning and better memory. They also
10 Cracking the Code of Life
The Mystery of the
Asthma Epidemic
If you don’t have asthma, several kids in your class
probably do. Asthma is the leading cause of school
absence in the U.S. It is a growing “epidemic” – yet
it’s not infectious. Asthma used to be rare, and it
probably didn’t affect stone age people at all. Oddly,
asthma runs in families, and there are a dozen genes
associated with it. Yet if it is genetic, why would it be
increasing so rapidly? Clearly, there are other
factors. Pollen, dust mites, stress, colds, air
pollution, and exercise can trigger asthma. Still,
didn’t our ancestors have stress and exercise
when they ran from predators? Yes, but
they didn’t have dust mites collecting in
their fluffy beds. They probably didn’t
have many colds (which thrive in crowds),
but they did have parasites like tapeworms. Our bodies react vigorously to gut
worms. This reaction is orchestrated by our
Immunoglobin E (IgE) molecule – which
also triggers asthma and allergies. We now
have such clean hygiene that we don’t
often get worms. But our IgE sentries are
still on the alert and they might mistake
dust mites and such for worms. If this
theory is correct, what was once a
“normal” genetic reaction that protected
us now causes us harm because of our
different circumstances.
Rescue and Recovery
The NMDA receptor part is just one piece of the puzzle about
how genes help build and operate the brain. If learning has a
genetic basis, what’s the role of education?
There are many reasons to do your mental pushups. The
brain is not a static piece of gray matter that is made once and
for all. It is continually being formed by your experiences and
sensations, which build and strengthen connections and crossconnections. Playing music builds one section of the brain;
debating buffs up another.
To learn more about the impact of the NMDA receptor on
learning, Joe Tsien developed a “knockout mouse” that lacked
part of the NMDA receptor in the part of the brain where
memories are formed (the hippocampus). In other words, he
took away some of the brainpower he’d added to the Doogies.
First he gave these new mice a mini-SAT and they didn’t score
very well! Then, he gave them “enrichment” and tutored them
in their skills. Upon re-testing, they scored just as well as the
normal mice. Not only that, the enrichment also
caused beneficial structural changes in their
brains, increasing the density of
their synapses – those connecabout it
tions that promote learning and
memory.
The moral of the story?
Exercise
your brain. Even if
Would it be right for
your
genetic
inheritance isn’t
people of normal learning
Ivy-league,
hard
work and
and memory capacity to
endurance
give
rewards.
A lot of
take “Doogie medicine” to
the connections that turn learning into memory happen at
night while you sleep – so get a good night sleep before your
exams! Also, other research shows that alcohol kills cells with
NMDA receptors, and the damage is much worse in teenagers
than in adults. Drinking can destroy 10% of a teen’s
brainpower. For better and for worse, how you live your life
affects how smart you are.
Think
!
make them geniuses – or
simply increase their
chance of getting into
Princeton?
Parietal Lobe
Frontal Lobe
Occipital Lobe
Temporal Lobe
Cerebellum
Hippocampus
Your World
11
Photo provided by National Geographic
Should we sacrifice
genetic privacy to
save lives?
In 874 AD, Ingolfur Arnarson threw parts of his
Norwegian throne overboard as his ship approached
Iceland and asked the gods to wash them ashore
where they wanted him to live. He became the first
Viking settler on this isolated island of geysers,
glaciers, and aurora borealis.
More Viking immigrants came until there were 20,000
“founders” in Iceland. Few newcomers followed. The population
numbers only around 275,000 today, and probably only 624,000
ever lived there. Most people are related and are on a first-name
basis. Even the phone book is listed by first names.
Today’s Icelanders are fond of epic tales of the Viking explorers,
and many of them proudly trace their family tree (pedigree or
genealogy) in precise detail back to an original settler. Studying
the ancestral genealogy is a national pastime. The family trees
always included notes on health, so a family can trace an inherited
disease back to a few ancestors who lived hundreds of years ago.
Because today’s Icelanders come from a small founder group,
certain diseases are very common in Iceland. For instance, a form
of arthritis (osteoarthritis) is five times more common here than
anywhere in the world.
Starting in 1915, during World War I, the government has
kept health records with the genealogies. During World War II, it
added tissues samples to these records, so today DNA from those
12 Cracking the Code of Life
samples can be studied. These records are so complete that 80%
of all the Icelanders who ever lived can be placed on a computerized genealogy – complete with health and genetic information.
This vast amount of genealogy data coupled with human
health history and the human genome sequence created an eyepopping genetic gold mine. In the landscape of the uniform
Icelandic genome, disease-causing variants of genes should really
stand out. Those variants can be cross-checked with health
history information. In fact, it was through Icelandic studies that
the Tay-Sachs and BRCA1 genes were first identified. Perhaps a
more systematic study of the Iceland genome will yield valuable
knowledge about diseases ranging from diabetes to schizophrenia. Perhaps such a study could jump-start the effort to develop
treatments – and save lives and suffering.
That was the reasoning behind the Icelandic parliament’s
1998 decision to make a deal with a private US company,
deCODE, which was founded by a native Icelander. The
parliament allowed the company to use existing health and
genealogy records to establish national databases and to develop
commercial treatments. All Icelanders, including babies at birth,
are automatically included in the database. If they want to be
excluded to protect their privacy, they must fill out forms in
several locations. Otherwise, information from every doctor’s
visit and every diagnostic test is entered into the database, and
computers analyze the DNA and the health of the patient’s
ancestors. That information can be used in the future, without
the patient’s knowledge. It can be used for further research. If it
leads to a profitable drug, the patient will not share the profits,
although Icelanders will receive drugs developed from this
database for free.
Endangered Health
Insurance?
Think
about it
!
Does this situation seem reassuring
Suppose you had a mole
or alarming? An international group of
removed and scientists
prominent scientists were so alarmed
used it for research
that they formed a group (called
without your knowledge.
Mannvernd, the Association of IcelandWhat if they discovered
ers for Ethics in Science and Medicine)
that you had a unique
to urge the repeal of the law. They
gene that prevented skin
argued that such data gathering violates
cancer and they became
international principles of privacy and
rich off a cancerhuman rights. Many doctors refuse to
prevention drug they
enter their patients’ data, protesting that
made with it?
it intrudes on patient/doctor privacy.
Internationally, many lawyers warn that
such a database could lead to discrimination and stigmatization
based on one’s genetic make-up. They predict the eventual
abuse of individual rights.
The storm over Iceland’s database is the most concrete
example to date of a new era of social and moral problems raised
by genomics. Where do we draw the line between what’s good
for medical science and what’s bad for people? How do we
balance the desire to protect privacy and to gather knowledge so
we can cure diseases?
Iceland, like many other countries, has a national health
care system and every citizen receives free (or subsidized) medical care. No one will lose health care if
genetic tests reveal a gene associated with a costly
disease or a shorter life span. The United States,
however, has a private health care system and people
already pay higher health insurance costs if
they have a “pre-existing condition” such
as heart disease. As genetic testing
becomes widespread, insurance
companies may want to see what
ultimate pre-existing conditions (that
is, genes) we all have. Will that
knowledge affect our access to affordable health insurance? Also, some
employers have used genetic
tests to determine who to hire –
and fire. Is it fair to be denied
insurance and jobs for something you cannot control, in the
same way you can’t control your
skin color or sex?
Career Connection: Ethicist: Help
society determine a fair policy towards the use of genetic
information that protects the individual.
Your World
13
Bruce Lahn’s curiosity about
how things work has followed
image to come
copy is too long, please cut
him from his native Anhui
Province in China to his position as an Investigator at the
Bruce T. Lahn
Howard Hughes Medical
Institute and a Professor of
Photo provided by
P
R
O
F
I
L
E
Human Genetics at the
University of Chicago.
A
Bruce T. Lahn: R
esearching the
Why of the Y
s a child in China, Bruce’s
favorite book was Ten
Thousand Questions, and he enjoyed taking
clocks and toys apart to discover their inner workings.
Such curiosity led him to major in Biology at Harvard
University and pursue a Ph.D. degree in Genetics at
MIT. As a graduate researcher, he worked in David
Page’s lab at MIT’s Whitehead Institute, studying the
“inner workings” of the Y chromosome as part of the
Human Genome Project.
This work helped explain a long-standing question:
why is the Y chromosome so small? Bruce summarizes,
“Genomics allows us to act like paleontologists and learn
about the history of the X and Y chromosomes. We
learned that Y and X started out like the 22 other
autosomal chromosome pairs. They were like two wellmatched candlesticks: same size, same genes.” In forming
a sperm or an egg (during meiosis), the two candlesticks
exchange pieces of DNA. This “recombination” serves as
a DNA quality check that corrects the destructive
mutations that naturally occur. Starting about 300 million
years ago, though, the X and Y went through dramatic
disruptions. The Y stopped recombining with the X.
Without recombination, genes on the Y began to decay or
disappear. Meanwhile, the X maintained its genes because
it recombined with its X partner in females. “Three
hundred million years without recombination has caused
14 Cracking the Code of Life
the Y to gradually but steadily decay,” Bruce reflects. “As a
result, today’s Y chromosome in humans is just a shadow
of its former self.”
In addition to contemplating why the Y shrank, Bruce
and his colleagues wanted to find out what made it still
tick. They showed that while most of the Y
chromosome’s genes have decayed, some genes persisted.
Many of the genes that survived on the Y were attracted
to it from other chromosomes. These genes play
important roles in giving males their male-specific
biological traits — the testis and the ability to make
sperm. “The fact that male fertility genes can persist in
the hostile environment of the Y chromosome means
they are crucial to our survival,” Bruce states. “But here’s
a puzzle: Why is Y a magnet for male fertility genes?
Maybe keeping them on Y prevents them from harming
females, who never inherit a Y. Maybe it protects
essential male genes from females, who could discard or
change them.” For Bruce, these questions are not just
idle curiosity. Understanding the Y may lead to cures for
male infertility or means of male contraception.
Besides pondering the Y, Bruce is also researching
brain development and evolution.
something
In the article on Tay-Sachs (pages 6-7), you read
that changes, insertions, or deletions in a gene’s
code can change the protein the gene normally
produces. In this activity, you can see for yourself
how a change in the gene’s “spelling” code changes
the “meaning” of its genetic sentence.
YouTry
can
Crack This Code!
Extension
1. Create your own code using
the four colors, write a
short sentence using that
code, and build a pop-it
bead chain of that sentence.
Give the key to your code
to another person or group
and have them decipher
your sentence.
2. Could the sequence on this
page be read backwards?
The DNA code is based on codons, which are sets of three
3. Can you create a code for
DNA letters. Each codon corresponds to one of twenty different
the 26 letter alphabet using
amino acids, which are strung together to build a protein chain.
groups other than three?
Any biology textbook has the “Standard Genetic Code” chart that
Why is the genetic code
shows which DNA codons match which amino acids. But we are
based on groups of three?
giving you our own code that you can use to build a chain of
colored pop-it beads (or gum drops or jelly beans which you can
attach with short pieces of
toothpicks). The four colors
represent the four DNA
Your World Code
chemical “letters.” Our code
r = red bead
g = green bead
y = yellow bead
will spell out actual words in
sentence, which symbolizes the
ggg: B
ggr: J
grg: I
grr: G
“meaning” of a gene, but it’s
gwy: Z
gyw: X
ryy: P
rgg: H
hidden in between some “junk,”
rrg: E
rrr: A
rrw: Q
rry: K
or non-coding, DNA.
ryr: L
wrr: S
wrw: U
wwr: V
To read this gene, see if you
yrr: M
yry: N
yyr: O
yyy: C
can match each three letter
codon to a letter of the alphabet
A-Z (which symbolize amino
acids). If the letters don’t match
a codon, they are “junk” DNA.
Hint: Find the “start” codon that
indicates the end of “junk” DNA
and the beginning of “coding”
DNA. Read until you get to a
“stop” codon, which signals the
end of the gene. What is the
sentence?
w = white bead
gry: W
rgr: F
rwr: R
www: D
gwr: Y
rgy : START
rww: T
wyg: STOP
DNA letters in a genetic sequence: Find the hidden sentence.
rwgrygrwgyrgygggrrrrryrrgrrryyyrrrrryrrgwygwyyrywrwgryg
Now read these four mutations and see how they change the meaning of the sentence.
Keep an eye out for deletions, additions, and single base changes.
Mutation 1: rwgrygrgyrgygggrrrrryrrgrrryyyrrryryrrgwygwyyrywrwgryg
Mutation 2: rwgrygrgyrgygggrrgrrryyyrrrrryrrgwygwyyrywrwgryg
Mutation 3: rwgrygrgyrgygggrrrrryrrwgrrrryyyrrrrryrrgwygwyyrywrwgryg
Mutation 4: rwgrygrgygggrrrrryrrwwygrrrryyyrrrrryrrgwygwyyrywrwgryg
Human
genes c
an be th
largest
ousand
about 3
s of bas
million, t
coding r
es long
he avera
egions (
(the
g
e
e
27,000
xons) c
coding s
a
)
n
,
and the
b
ections
ir
(introns e separated by
much m
)
lo
.
ore eas
ng nonComput
ily than
ers can
you can
decode
!
DNA
Adapted from an activity developed by former middle school teacher Patti Soderberg
and Dr. Michael H. Patrick, Department of Medical Genetics, University of WisconsinMadison for the Wisconsin Teacher Enhancement Program.
Your World
15
Expand Your Knowledge
The Biotechnology Institute is
a not-for-profit organization
dedicated to education and
research about the present and
future impact of biotechnology.
Its mission is to engage,
excite, and educate as many
people as possible, especially
young people, about
biotechnology and its immense
potential for solving human
health and environmental
problems. The Institute thanks
the following sponsors for
financial support of its
activities for 2000-2001.
e
m
o
s
o
m
o
r
h
C
#
The “trading card” to the right
mentions just some of this
17
chromosome’s statistics and
importance to the game of human
Highlight
es
aller chromosom
• One of the sm
life. Of course, many of the plays
Key Roles
s
• Taste receptor
ne
ge
ir
pa
• P53 re
and fouls involve players on other
chromosomes as well. Research
Foul Plays
t cancer)
• BRCA1 (breas
y
sease susceptibilit
Di
’s
• Alzheimer
cy
ien
fic
de
e
• Growth hormon
ophy
• Muscular Dystr
)
osomal recessive
• Deafness (aut
another human chromosome and
AVANT Immunotherapeutics
Aventis
BIO
create a card to trade with your
friends and classmates. Collect a
Connetics Corp.
CV Therapeutics
Ernst & Young
whole set of chromosomes and learn
more about your genome.
Feinstein Kean Partners
Start your research with these sites from the
Human Genome Project:
Fisher Scientific
http://www.ornl.gov/hgmis/posters/chromosome/
http://www.ncbi.nlm.nih.gov/disease/
http://www.ncbi.nlm.nih.gov/genome/guide/human
Genencor International
InterMune Pharmaceuticals
MDBio, Inc.
Monsanto Fund
Neose Technologies, Inc.
Novartis Foundation
Onyx Pharmaceuticals
Pennsylvania Biotechnology
Association
Pfizer Inc.
Sangamo BioSciences
Scottish Enterprise
U.S. Department of Commerce
U.S. Department of Energy
Utah State University
Build Your Database
www.BiotechInstitute.org
Cartoons about Genomics: http://cagle.slate.msn.com/news/gene/
Celera’s education site: http://www.genomenewsnetwork.com
Chromosome Maps - http://genome.ucsc.edu and UCSC and http://www.ornl.gov/
hgmis/launchpad.
DeCODE - http://www.decodegenetics.com/
Discover, “Getting Stupid,” by Bernice Wuethrich, March, 2001(Teens and Drinking).
Genome: The Autobiography of a Species in 23 Chapters, by Matt Ridley.
Human Genome Program: (DOE) http://www.ornl.gov/hgmis and (NIH) http://
www.nhgri.nih.gov
Mapping the Icelandic Genome - http://sunsite.berkeley.edu/biotech/iceland/
Nature, “Special Issue: Genome Gateway,” February 15, 2001.
Newsweek, “Decoding the Human Body,” April 20, 2000.
New York Times Genomics web site - http://www.nytimes.com/library/national/science/
genome-index.html (Diagrams and articles).
NOVA “Cracking the Code of Life” episode, Spring 2001. - http://www.pbs.org/wgbh/
nova/genome/
Science, “Special Issue: The Human Genome,” February 16, 2001.
Scientific American, “Building a Brainier Mouse,” by Joe Tsien, April 2000; “In Focus
(Asthma): The Invisible Epidemic,” November 1999; “Why the Y is so Weird,” by
Karin Jegalian and Bruce T. Lahn, February 2001.
Sequencing DNA (animation) - http://www.msnbc.com/news/528553.asp.
Time, “The Race is Over,” July 3, 2000.