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Volume 12, Issue No. 2
About This Issue...
Dear Reader,
The accumulated work of many scientists, including
Rosalind Franklin’s X-ray crystallographic picture of DNA,
provided the clues that led two men to write an article in
the April 25, 1953, issue of Nature that humbly began,
“We wish to suggest…” What did James Watson and
Francis Crick suggest? That they had found the secret of
life—the structure of the molecule that carries hereditary
traits for all living things, deoxyribonucleic acid!
In turn, Watson and Crick’s work provided the foundation
for an explosion of knowledge about DNA, obtained
through many tools. This issue offers an overview of the
progress made in unraveling the secrets of the human
genome. We examine how proteins are made, genetic
testing, DNA fingerprinting, personalized medicine, and
the role of mathematics in genetics.
In this issue, you will also glimpse the ethical implications
of this work. We hope that it will help you make informed
decisions about the way these discoveries can be applied.
Some of you will become the scientists of tomorrow,
working on questions that we can’t even imagine today.
All of you, however, can play a role in how society will use
biotechnology in everyday life.
Sincerely,
Paul A. Hanle, President
Biotechnology Institute
2
The Secret of How Life Works
Researchers would get laughed at if they showed
up for work with a Sherlock Holmes cape and hat, but
scientists are indeed detectives, solving mysteries.
People have asked questions about
life throughout the ages: How are babies
made? Why are children so similar and yet
so different from their parents? Why do
some people live to be 100 while others die
young? Why do we get sick?
And they’ve certainly come up with
ideas. For example, in 100 AD, Romans
speculated that horses could be fertilized by
the wind. From 1100 to 1700, “spontaneous
generation” was a popular explanation for
organisms springing forth from nonliving
matter. Maggots, for example, supposedly
arose from horsehair.
Motivated by a desire for knowledge,
today’s scientists sift through physical
evidence to make a case to explain “why”
and “how.” A clue here. Evidence there.
Sometimes building on the work done in
altogether different fields, they develop both
the ideas to be tested and the tools they
need to do so.
Having the evidence, however,
doesn’t always close the book on a
case. People were using biotechnology—manipulating living matter to
solve problems or create useful products—to make beer, wine, and bread,
and to breed plants and animals, before
they had a clue about the “why.” Likewise, Gregor Mendel explained in 1865
how traits are inherited, but his work
was ignored for 35 years. Then three
scientists, working independently, picked
up the trail in 1900.
Today we understand more about how
heredity works. We’ve pieced together amazing connections, from
cell to nucleus to chromosome
to gene to the double helix of
DNA (deoxyribonucleic acid).
Our genetic information
contains the recipes for proteins.
Now, some scientific sleuths
are studying genomics (the study
of genes and their function) and
proteomics (the study of proteins—their
locations, structure, and function).
During your lifetime, researchers
have sorted out some of the genes that
affect people’s ability to stay healthy, such
as tendencies to gain weight, suffer heart
conditions, and get cancer. They’ve also
uncovered some genetic markers linked to
personality traits.
Scientists can analyze your genetic
profile, but the complete picture of
heredity—and how we should treat many
genetic conditions—is still a mystery.
Scientific detectives have opened doors of
understanding, but they have much more to
explore. Young, creative minds are always in
great demand in the sciences. Become a scientific detective and see how much more you can
unravel about “the secret of how life works.”
—Lois M. Baron
© A. Barrington Brown/PhotoResearchers
Our first understanding of heredity is credited to Gregor
Mendel’s curiosity about how traits were passed through
generations of peas.
The year 2003
marks the
50th anniversary
of Crick and
Watson solving
the puzzle of
DNA’s structure.
Contents...
The Case of the Sleuthing Scientists........................ 2
Cooking Up Proteins .............................................. 4
Math Matters .......................................................... 6
Testing What We’re Made Of .................................. 8
A New Kind of Fingerprint ....................................10
Pharmacogenetics: Tailor-Made Medicine ..............12
Profile: Forensics at Work: DNA Analyst ................14
Activity: The Case of the Crown Jewels ..................15
‘DNA’s Dark Lady’ ................................................ 16
Resources ............................................................. 16
Biotechnology & You
Volume 12, Issue No. 2
Publisher:
The Biotechnology Institute
Editor in Chief:
Kathy Frame
Managing Editor:
Lois M. Baron
Writing (Except Where Noted):
The Writing Company
Cathryn M. Delude and
Kenneth W. Mirvis, Ed.D.
Advisory Board:
Dena S. Davis, Ph.D., J.D., Cleveland
State University Law School
Don DeRosa, Ed.D., CityLab,
Director of Education,
Boston University Medical College
Lori Dodson, Ph.D., North Montco
Technical Career Center
Anthony Guiseppi-Elie, Sc.D.,
Virginia Commonwealth University
Lynn Jablonski, Ph.D.,
GeneData (USA), Inc.
Design:
Snavely Associates, Ltd.
Philip R. Reilly, M.D., J.D.,
Interleukin Genetics, Inc.
Mark Temons,
Cover Art:
Williamsport High School
Virginia Commonwealth University
Sharon Terry, M.A., President,
– Creative Services
Genetic Alliance
Photos: U.S. DOE Human Genome
Theodore Torphy, Ph.D.,
Program <http://www.ornl.gov/
Centocor, Inc.
hgmis> and Photos.com
The Biotechnology Institute is an independent, national, nonprofit organization dedicated to education and research about biotechnology. Our mission
is to engage, excite, and educate the public, particularly young people, about
biotechnology and its immense potential for solving human health, food, 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 the Biotechnology
Institute for information on subscriptions (individual, teacher, or library sets).
Some back issues are available.
Copyright 2003, Biotechnology Institute. All rights reserved.
For more information:
Biotechnology Institute
1840 Wilson Boulevard, Suite 202
Arlington, VA 22201
Phone: (703) 248-8681
Fax: (703) 248-8687
[email protected]
The Biotechnology Institute
acknowledges with deep gratitude the
financial support of Centocor, Inc., and
Ortho Biotech.
The Biotechnology Institute would
like to thank the Pennsylvania
Biotechnology Association, which
originally developed Your World, and
Jeff Alan Davidson, founding editor.
The issue of Your World, “The Secret of How Life Works,” complements two
programs: Our Genes/Our Choices, one of the PBS/Fred Friendly Seminars
(http://www.pbs.org/fredfriendly/ourgenes/), and the touring Pfizer exhibit
“Genome: The Secret of How Life Works” (http://www.wl.com/subsites/
philanthropy/caring/science.education.museum.genome.html).
Your World
3
People often compare a gene to a recipe. A recipe
contains the instructions for preparing a specific
dish. A gene contains the instructions for making a
specific protein. Let’s pretend the
genome—all the genetic information
in a cell—is a recipe book.
Imagine that the genome is a giant
book with about 30,000 recipes, and each
gene is one specific recipe. Nothing
happens if the book just stays on the
shelf. A cell (our kitchen chef) must open
the book to a specific recipe and start
following the instructions.
Each cell gets a complete recipe
book (genome) regardless of what tissue or
organ it belongs to. Likewise, just as the
genome is the cookbook, the
proteome is the complete selection of proteins an organism can
produce, much like all the dishes
you can make from that cookbook. However, depending on the
cell’s job, the cell activates only
some of the recipes to make only
some of the proteins. For example,
the liver processes toxins found in our
bodies. So liver cells produce different
proteins than skin cells, which protect
us from the outside world. ■
4
The Secret of How Life Works
Revised Recipes and
Diverse Dishes
Occasionally, a recipe in the genome book might have
a misprint in it. Most of the time, a misprint doesn’t
affect the final dish at all, but sometimes it changes the
way the dish will look or taste. Those changes can be
good (like adding chocolate chips to plain cookies)
or bad (like substituting broccoli for sugar). Such
misprints in our genome are called mutations.
They are caused when some DNA bases (adenine,
cytosine, guanine, and thymine) are changed,
added, or deleted. Most mutations don’t affect us at
all, but some can cause a disease or disorder. Other
times, though, the variations can make for
happy surprises. It is important to understand that the word mutation doesn’t
apply just to things that go wrong. Scientists also use the word to mean all
the different variations that make us
so diverse and interesting. Without
variations, everyone would look exactly the same, and our species could
not evolve and adapt to new environments. Every person’s genome has
millions of genetic variations that
make each of us unique.
© Bruce Cramer
Here’s how a cell (chef) might go about making a particular type of protein (cookie).
Getting the work order: Cells begin to make a cookie (protein)
when they get a work order. Cells send messages (molecular
signals) to themselves and to others. They can also pick up
signals from the outside world. Some of those signals tell the
cell it needs to produce a particular protein.
Finding the right page: The cell needs an index to find the right
page for the recipe (gene) in the book. A special protein in the cell
called an enzyme helps out. This page-finder enzyme is
called RNA polymerase, and it looks for information
that marks the beginning of a specific recipe.
Reading the recipe: When the enzyme finds
the right recipe, it starts to read it. It
chugs down the long DNA chain like
a train on a track. When it meets
a stop sign (stop codon), it has
reached the end of the recipe. This
DNA track is made of four chemical
bases—adenine, cytosine, guanine,
and thymine—which are known by their
initials A, C, G, and T. As the RNA polymerase
chugs along, it transcribes the important parts to a recipe
card. This recipe card is known as messenger RNA (mRNA).
When the mRNA leaves the nucleus, it contains an edited version
of the gene’s recipe, with just the essential instructions.
Going to the kitchen: The mRNA chain goes to the kitchen, the
ribosome, which will combine the individual ingredients to make
the cookie dough.
Making the dough: The ribosome reads
the mRNA, three letters at a time.
Those triplets are the ingredients list.
For each triplet, the ribosome grabs
the listed ingredient, which is one
of 22 amino acids. It attaches each
ingredient to the next, creating a
chain of amino acids.
Baking the cookie: With the last
ingredient in place, the amino acid chain
peels off. It is still an immature protein, like
raw cookie dough that needs to be shaped and
baked. A chaperone protein rushes over
to show the immature protein when and
how to fold into a three-dimensional
shape. When the chain takes on the
right shape, it is a mature protein, like
a baked cookie. The protein’s shape will
determine how it interacts with other
proteins and molecules.
Those interactions
define how the
protein functions in
the body.
Your World
5
flower with a showier bloom, a cow that produces
more milk, a strain of wheat that resists disease,
or a dog that searches out rats?
For thousands of years, farmers, herders, and others have been
selectively breeding plants and animals to create more productive
or desirable hybrids. But it wasn’t easy to predict results. It took
a remarkable combination of careful experiments and cleverly
applied mathematics by 19th-century scientist Gregor Mendel to
reveal what was going on.
Nowadays, mathematics continues to be a crucial tool as
scientists strive to understand the details of the genetic molecular
code that not only defines what happens during breeding but also
guides many aspects of plant, animal, and human life.
T
TT
t
Tt
T
© Leslie Holzer/PhotoResearchers
Interested in having a horse that runs faster, a
Pass the Peas, Please
About 200 years ago, many scientists
believed that children were a blend
of their parents’ traits. Gregor Mendel
(1822–1884), a monk in Central Europe, put that idea to the test using peas
as the model organism.
Between 1856 and 1863, Mendel
cultivated and carefully observed some
Mendel is called the
28,000 pea plants. He examined this
father of genetics because
huge amount of data for patterns. For
his carefully controlled
experiments revealed how
instance, when he cross-pollinated
traits are inherited.
plants that produced just yellow seeds
with those that produced just green seeds, he found that the
first generation always had yellow seeds. But in the following
generation, about three-quarters consistently had yellow seeds
and one-quarter had green seeds. This 3:1 ratio also appeared
for flower color and other traits.
Mendel concluded that each trait is determined by factors
(now called alleles) that are passed on to descendants unchanged,
not blended. An individual inherits one such factor from each
parent for each trait. Moreover, even though a trait may not show
up in an individual, it can still be passed on to the next generation.
A strong believer in Mendel’s theories, biologist Reginald C.
Punnett (1875–1967) invented a handy way to work out the ratios
of allele combinations and what traits show up (are expressed)
with these combinations. Known as the Punnett square, this tool
helps predict the outcomes of simple breeding experiments in
certain genetic studies. (Of course, there are exceptions to the rules
that Mendel formulated.)
Stringing Genetics Along
tT
tt
© Bruce Cramer
t
If each parent has a dominant and a recessive gene for a single-gene trait, the chances
are three to one that each child will exhibit that trait. But it is possible for all the
offspring to exhibit the trait—or for none of them to show it—because the odds are
calculated independently for each one (see box, p.7).
6
The Secret of How Life Works
Discovering DNA’s structure opened up new avenues of
exploration and new opportunities for applying mathematics.
Human DNA consists of 3.2 billion base pairs—each one a
piece of data inherited from your parents. Called the genome,
this information provides instructions for assembling molecules
(mainly proteins) and controlling when and where cells make
these parts. In recent years, scientists have sought to decipher
the plans by sequencing the human genome—identifying and
locating every base of the immensely long strands that make up
chromosomes.
What Are Your Chances?
Emilo has four brothers and no sisters. His mom is expecting another
baby. What are the chances that he will have a sister? Another brother?
The key word is chance. You see the outcomes of chance every day. A coin toss
before a ballgame determines who gets the ball first. What are the chances that your team
will have the ball? The possibilities are heads and tails: two choices. So your chance of calling
it correctly with each toss is one in two. When you toss the coin the next time, you still have the
same possible outcomes: heads or tails. The outcome of the second toss has no connection to the first
toss. The same is true in Emilo’s case. The outcome will be independent of the previous ones, so he has an
equal chance of getting a sister or another brother.
Another example is dice. What are your chances of rolling a die and getting a “1”? How many possibilities
are there when you throw a die? Six. So, your chances would be . . . one in six.
—Kathy Frame
Sequencing a genome is like assembling an enormous jigsaw
puzzle. The genome is cut into tiny pieces, which are then individually sequenced. The millions of pieces must then be put back
into the correct order. That’s where mathematics comes in.
Computer programs do the assembly work. They typically
consist of a set of mathematical steps that sort, edit, and combine
fragments. Normally, the easier steps are done first, followed
by the harder ones. It’s like first organizing puzzle pieces
according to color, then working
on the easiest-to-see patterns.
It’s tricky. In the human
genome, many DNA sequences are repeated many
times over, so one region
can easily be mistaken for
another when the sequence
is assembled.
So far, researchers have
sequenced the human
genome and those
of some plants and
animals, including
certain bacteria
and viruses,
mosquitoes, rice,
and mice. Trying
to understand
what different
parts of a sequence
do, they again use
mathematics to sort
through the jumble
of bases and compare
genomes of different
organisms.
For example, scientists have started comparing the human
genome with the mouse genome. To their surprise, they found
many more shared sequences than they expected.
Mathematical tools help geneticists identify such similarities.
One useful approach is to quantify how much one sequence
differs from another.
Here are two sample strings of DNA lined up on top of one another. Each letter represents one of the four bases making up DNA.
agctttcgtgag
acgtttccagagtc
One simple measure of similarity is to count the number of
changes needed to convert one string into the other. For the
first string, the answer is six: four substitutions of one letter for
another and two insertions of additional letters to make it match
the second string. Such numbers help specify how similar one
sequence is to another. More complicated mathematical schemes
help characterize similarities among three or more sequences.
Driving Each Other
Today, mathematicians and geneticists continue to use
their skills to expand our knowledge of genetics. Some write
computer programs to locate the genes along a strand of DNA
or use the sequence of a gene to predict the structure of the
protein it creates. Others are developing theories to account for
the way DNA twists and coils. Still others are trying to answer
questions about how the genetic code evolved.
Mathematical techniques allow geneticists to expand their
understanding of genetics. This new information raises
questions that prompt mathematicians, in turn, to refine their
techniques, develop theories, and embark on new research. ■
—Ivars Peterson
Your World
7