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Vol. 14, No.

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A magazine of biotechnology applications in health care, agriculture, the environment, and industry Vol. 15, No. 1
Contents Biotechnology is spending time and money on trying to figure out why kids
and adults are heavier, on average, than previous generations. Heavy teens often
Biotechnology Tackles Obesity . . . . . . . . . . . . . . . . . . .2 become heavy adults, and those who weigh 40 percent more than their ideal
Getting Inside What Determines Weight . . . . . . . . . . .4 weight are prone to health problems, making health officials and policymakers
anxious. To help combat obesity, biotech researchers are figuring out what parts
Calorie-Coated Diabetes . . . . . . . . . . . . . . . . . . . . . . .6 of the human genome control weight, developing ways to control weight, and
The Roads to Controlling Obesity . . . . . . . . . . . . . . . . .8 searching for treatments to deal with obesity-related illnesses, such as diabetes.
Made-to-Order Diets . . . . . . . . . . . . . . . . . . . . . . . . .10 In this issue of Your World, we take a closer look at biotechnology’s involvement
How Low Should You Go? . . . . . . . . . . . . . . . . . . . . .12 in the complex issue of obesity. Keep in mind these main points:
Career Profile: Learning from Fat Mice . . . . . . . . . . . .14 ● Obesity has genetic components.
Lab: Leptin to the Rescue? . . . . . . . . . . . . . . . . . . . . .15 ● Biotechnology is exploring the human genome for ways to control weight.
● Nutrigenomics might help us choose our diets based on genetic makeup.
Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16
● Regardless of your genes, eating and exercising carry a lot of weight in how
heavy you’ll be as an adult.
As always, we hope you enjoy the magazine. We also hope it inspires you to
choose a career in the exciting world of biotechnology.

The Biotechnology Institute is an independent, national, nonprofit WHERE FAT


organization dedicated to education and research about the IS FOUND
present and future impact of biotechnology. Our mission is to Fat tissue is found
engage, excite, and educate the public, particularly young Paul A. Hanle throughout the body,
people, about biotechnology and its immense potential for solving President
human health, food, and environmental problems. Published mostly underneath
Biotechnology Institute the skin but also in
biannually, Your World is the premier biotechnology publication
for 7th- to 12th-grade students. Each issue provides an in-depth deeply seated areas,
exploration of a particular biotechnology topic by looking at the as on some
science of biotechnology and its practical applications in health
care, agriculture, the environment, and industry. Please contact
ADIPOSE TISSUE (FAT CELLS) internal
organs.
the Biotechnology Institute for information on subscriptions (indi- Fat plays important roles within our bodies. We store energy
vidual, teacher, or library sets). Some back issues are available. in the form of fat, which acts as a nutritional reserve. Fat also
absorbs shocks to protect internal organs,
insulates our bodies against cold, and Hair
in some cases, produces heat.
Glycerol
Vol.15, No. 1 Fall 2005
Publisher The Biotechnology Institute HOW FAT IS PROCESSED FROM FOOD Fat cell Connective tissue
Editor Kathy Frame Fatty acid
Managing Editor Lois M. Baron
1. Food containing fat enters the
Designer/Illustrator Diahann Hill stomach. Stomach acid helps 1 Muscle
prepare food for the digestive
Cover, p. 3 photogaphs: Mirrorball Studio/Jason Horowitz
process that takes place
Advisory Board in the intestines. Most
Don DeRosa, Ed.D., CityLab, Boston University School of Medicine fat in food exists as
Lori Dodson, Ph.D., North Montco Technical Career Center, Landsdale, Pa. triglycerides. Liver
Lucinda (Cindy) Elliott, Ph.D., Shippensburg University, Shippensburg, Pa. 2
Lynn M. Jablonski, Ph.D., GeneData, Waltham, Mass. 2. Once in the intestines,
Noel Mellon, Mt. Carmel High School, San Diego, Calif. bile salts from the gall- Stomach
Mark Temons, Muncy Junior/Senior High School, Muncy, Pa. bladder help break up
Carolyn A. Zanta, Ph.D., UIUC-HHMI Biotechnology and Educational large droplets of fat into
Outreach Program (BEOP), Urbana, Ill. smaller particles.
Acknowledgments Gallbladder Pancreas
The Biotechnology Institute would like to thank the Pennsylvania
Biotechnology Association, which originally developed 3. The fat particles are broken
Your World, and Jeff Alan Davidson, founding editor. down further by special
pancreatic enzymes
For More Information 3
Biotechnology Institute
called lipases. The
Intestinal cell Lymph
1840 Wilson Boulevard, Suite 202
resulting fat cell
component—glycerol vessel
Arlington, VA 22201
and fatty acids—are Intestines
info@biotechinstitute.org
Phone: 703.248.8681 Fax: 703.248.8687 small enough to be
absorbed by intestinal cells.
© 2005 Biotechnology Institute. All rights reserved.

The Biotechnology Institute acknowledges with deep gratitude 4. In the intestinal cells, triglycerides are
the financial support of Centocor, Inc., and Ortho Biotech. formed and coated by a protein. These
are called chylomicrons. The coating
helps them dissolve faster in water. 4
Too big to pass through capillaries,
the chylomicrons enter the lymphatic Chylomicron Used with permission
system, where veins provide access to of the Milwaukee
the bloodstream. Journal Sentinel

2 Biotechnology and OBESITY


BIOTECHNOLOGY TACKLES Obesity
WHAT IS BIOTECHNOLOGY we each crave, and how each body
responds to exercise and diet. JUST USE
DOING TO ADDRESS OBESITY?
Our understanding of how genes YOUR NECK
High school senior Danielle Alvara-
affect weight gain is still in its infancy.
do grabs some cream-filled chocolate A neck measure-
The first fat-regulating gene, leptin, ment is just as
swirls, bread pudding, and Jell-O for
was discovered only 11 years ago. accurate as the
breakfast. Her favorite lunch is a
Today, researchers estimate that up BMI in
cheese sandwich or two with bacon
to 340 different genes are involved in determin-
bits. Dinner usually includes red meat, ing whether
determining weight. Differences in
though sometimes Danielle opts for people are over-
these genes may account for 50 to 70
pizza instead. weight. In the healthy weight
percent of the variations in obesity range, men have necks of less
Medical experts blame such high-
among the people around us. than 37 cm (14.6 inches) circum-
sugar, high-fat, high-salt foods for
ference; and women’s necks are
making people fat. Yet Danielle THE SIZE OF THE PROBLEM less than 34 cm (13.4 inches) around.
never gains an ounce. The number of obese Americans has http://newswise.com/articles/view/27231/
The answer to this riddle lies in our doubled over the past 20 years to near-
BMI FOR CHILDREN AND TEENS:
genes. They contain the master plan ly one out of every three adults. While http://www.cdc.gov/nccdphp/dnpa/bmi/bmi-for-age.htm
that regulates how fast our bodies burn there is no accepted definition for
energy and store fat. They determine obesity in adolescents, about one out
when each of us is hungry, what foods of every seven American adolescents
is considered overweight. Researchers Health officials have long linked
MEN: “Apple” shape WOMEN: “Pear” shape have been trying to figure out why so BMIs above 30 with increased chances
Chest Breasts many people are now heavier. of high blood pressure (which may
Waist The most common measure of cause a stroke), heart disease, dia-
obesity for adults is the body mass betes, and even some relatively rare
Abdomen Hips index (BMI), the ratio of weight divided types of cancer.
Buttocks Buttocks by height squared. (To find your BMI, Yet some of these links are being
multiply your weight in pounds by rethought today. While few doubt
Sex hormones influence where fat is
deposited. The most common locations 704.5 and divide by your height in severe obesity leads to illness, med-
for each gender are shown above. inches squared.) ication and exercise allow many obese
A BMI above 25 is defined as over- people to live healthy lives. In fact,
weight, above 30 as obese, and above recent surveys suggest that adults
TWO KINDS 40 severely obese. A man 5 feet, 6 who are moderately overweight are
OF FAT CELLS likely to live longer than those in the
inches tall, for example, would be
Mitochondria overweight at 155 pounds, obese at “healthy” weight category. Claims in
WHITE CELL BROWN CELL 186 pounds, and severely obese at a report from the Centers for Disease
Important in energy Important for generating 247 pounds. Control and Prevention that 300,000
metabolism, heat heat. Found mostly in Americans die prematurely from obe-
insulation and infants, and the supply HOW THE BODY BURNS FAT sity proved grossly exaggerated upon
cushioning. shrinks as the person The body’s first choice for energy is from
ages. a closer look at the data.
glucose. The second choice is carbohy-
drates. After those, the body breaks Researchers are turning to biotech-
down fat reserves. Fat again becomes nology to understand the genetic
FAT CELL fatty acids and glycerol. But this time, it mechanisms that cause obesity and
IN THE BODY can be broken down further for energy.
affect health. Genetics is a powerful
Glycerol can be released to the blood-
Glucose and stream, where, drawn by tool for tracing how the parts of the
Fatty acid amino acids Fatty acid Glycerol the liver, it is con- metabolic system interact with one
verted to glucose, another. By mapping these mecha-
then to energy.
nisms, researchers hope to one day
BLOODSTREAM explain how people like Danielle
HOW THE BODY STORES FAT Alvarado remain thin on diets that
Once in the bloodstream, chylomicrons are broken into fatty acids by enzymes called fatten the rest of us—and develop
lipoprotein lipases. This enzyme is controlled by insulin. When more insulin is generated, treatments for obesity-related diseases
more lipoprotein lipases are available to process chylomicrons. As fatty acids are drawn
into fat cells, the insulin helps congeal fat molecules into droplets. Fat cells can store fat
and perhaps even obesity itself. Keep
directly or convert carbohydrates or protein to fat for storage. But the conversion process reading this issue of Your World to
requires ten times the energy of direct storage of fat. find out more details! —Alan Brown
Your World 3
STEVE GSCHMEISSNER/SCIENCE PHOTO LIBRARY

What genes are involved


in whether we’re thin or fat?
What makes people obese? burn more calories; when they eat suggest that 40 to 70 percent of
The simple answer is that our less, their bodies turn down the heat. their obesity was inherited.
bodies are wired to put on fat. When This regulatory system works so Unfortunately, our understanding
humans had to hunt and forage for well, adults in the Western world gain of the genetics that regulate obesity
food, daily meals were never a sure only about 0.5 to 1.0 pound annually. is still sketchy. Only in the past
thing. Our bodies evolved to consume This is equivalent to eating one more decade, starting with the identifica-
rich foods high in calories and store Ritz cracker per day than the body tion of the gene that makes the
the excess energy as fat. When food can metabolize. hormone leptin, have scientists
was scarce, we burned fat for energy. Yet some people remain thin and begun to unravel how the body
Today, where daily meals are others grow obese. This has to do regulates fat storage. While hun-
a given and high-calorie foods are with their genetic programming: some dreds of genes play a part is this
plentiful, our bodies still behave as people are genetically disposed to complex process, only a few of
they did thousands of years ago: store fat more easily than others. the chemicals they make have
they tell us to eat rich foods and Scientists know this because they major roles.
store the excess calories as fat. found a way to separate the influence Insulin is one of them. The
So why don’t we just keep getting of genes from such environmental pancreas makes insulin when it
fatter? factors as eating and exercise habits. detects the presence of the sugar
It turns out that every body has a They investigated identical twins glucose from food. The body
target weight range and will regulate adopted by different families. Since treats glucose as pure fuel, and
itself to remain there. Obesity the twins had identical genes, only insulin regulates how fast its
researchers typically find their sub- their environment differed. In terms cells burn or store that fuel.
jects have difficulty losing or gaining of obesity, the twins more closely A second hormone, leptin,
weight. When they eat more calories, resembled each other than the families is produced in fat cells. It sig-
their metabolism speeds up and they that brought them up. These studies nals that the body has stored

4 Biotechnology and OBESITY


1 2 energy as fat. When leptin levels rise high enough, they suppress appetite. They
TNFRSF1B
PGD
36.3
36.2
ACP1 25 also work with insulin to regulate metabolism. Babies born without the ability to
APOB 24
Dob1
36.1
Qlw12
23
make leptin are constantly hungry and become severely obese.
35 POMC
Wokw2
D1S193
34.3
34.2
34.1 D2S165,367 22 Afw2 Scientists are currently investigating about 60 chemicals that help control weight
200,476
SSC6q
33
32
D2S1788 21
gain. Ghrelin, for example, is the most prominent of more than 20 chemical agents
16

15
that make us hungry. Ghrelin rises between meals and declines when insulin and
LEPR 31
ALMS1
14
13
leptin levels rise.
Nidd3nsy
D1S550
22
Bw6e 12 Evidence suggests that imbalanced diets may interfere with chemical processes
SSC6q IGKC
Qbw1 ADRA2B 11.2
that tell us when we’ve had enough to eat or possibly even what to eat. Eating fat,
Hlq3/4 21
Qlw1 11.2
12 Pfat1 for example, does not reduce ghrelin levels—and appetite—as fast or as much as
HSD3B1 13

12
13
14.1
eating protein or sugar. Fructose, a sugar commonly used to sweeten soda and
Afp2
14.2
14.3 baked goods, does not suppress hunger as well as glucose, a product of bread
12 21
and starch digestion. Rats fed fatty diets grow less sensitive to leptin over time.
LMNA 22 Fob1
FPLD
21
23
The more scientists dig, the more metabolic mysteries they unearth. They have
22 FAT1
Obq2 23
BFM4 24 found that obese people lose their sensitivity to leptin, but cannot explain why.
Obq3
ATP1A2/B1 24
25 BBS5 31 They know that many obese people fail to produce enough insulin and become
Nidd6
32 diabetic, yet cannot explain how this happens.
31
Mob7
Bw6a
Mob6 33 Nidd5 Clearly, we are genetically programmed
Afw1
32 Afp1
Obq2
34 to put on fat. Yet we are years
Mighty Mouse
35
Hlq1
41
Qlw13
IRS1 36 away from understanding
Batq2
42
AGT
37 why one person gains
Afw3
Nidd/gk6
43
44 255 Mb weight on the same Scientists believe that 100 or more genes
236 Mb
diet that leaves make agents that control obesity. Each one interacts
Y X with other body chemicals in countless ways. The only
11.0
11.2 22.3
another slim.
Fob4
11.21
11.22
22.2
22.1
SGBS2
—Alan Brown way to unravel those mechanisms is to eliminate one gene at
11.23
MEHMO 21.3
21.2
a time and observe what happens.
22
21.1
Bw3
28 Mb
11.4 Since 1987, scientists have been able to do this by “knocking out”
11.3
MRXS7 11.1 genes in mice. The results have given us new insights into obesity.
11.2
12
In 1999, Canadian researchers knocked out the gene that makes
WTS 13
Bw2 the enzyme PTP-1B. The modified mice resisted weight gain even when
fed a very high-calorie, high-fat diet.
21
CHOD
SSCX
Bw1
The same proved true when University of Wisconsin scientists
22
23
knocked out the gene that produces SCD, an enzyme that helps mice
HTR2C
DXS6804
24
25
make body fat. The change also boosted mouse metabolic rates.
GPC3,4
BFLS
26 SGBS1
FGF13
In 2005, Washington University researchers modified the abili-
QbwX
SMRXS
27
ty of skeletal muscle to metabolize fat and created mice that can
Obq6 28 Fob4
164 Mb
grow fat but resist diabetes.
In each case, scientists hope to develop drugs that
Above: Four chromosomes from

ALFRED PASIEKA/SCIENCE PHOTO LIBRARY


target these enzymes in order to fight diabetes and
the Human Obesity Gene Map.
Every year the map compiles all
obesity. —A.B.
markers, genes, and mutations
associated or linked with obesity.
See http://obesitygene.pbrc.edu/.

Right: B-chain of Insulin Molecule


An insulin molecule is made up
of two chains of amino acids, the
A and B chains, held together by disul-
phide bridges. This computer graphic of
part of the B chain shows carbon atoms
as green, oxygen as red, and hydrogen
as blue. Lines represent atomic bonds.

Your World 5
Calorie-Coated Diabetes
What is biotech doing to
prevent and treat diabetes?

GUSTO/SCIENCE PHOTO LIBRARY


Hold the soda! It may taste good glucagon rise, signaling the liver to glucose levels, making them too high
now, but soda pop is one of the biggest release sugar. or too low. When this happens, you
contributors of calories—as sugar—to Types of Diabetes might feel sleepy, dizzy, confused,
the average American diet. And too In type 1 diabetes, the body’s or have blurred vision.
much of it increases the risk of gain- immune system destroys the insulin- This may not be serious when
ing weight and developing diabetes producing beta cells in the pancreas. you’re listening in class, but it could
later in life, according to a study of With type 1 diabetes, people get be fatal when you’re driving. If your
91,000 nurses out of the Harvard insulin through shots or a pump so blood glucose level is too low, you
School of Public Health. they can process sugar. might make bad choices, not focus on
Sugar itself is not bad. In fact, it’s In type 2 diabetes, the body pro- your driving, or lose control of your
the basic source of energy for your duces insulin, but not enough or the car. Long-term complications can lead
body. Without it, your cells would not cells can’t use it well. Of people with to blindness, heart disease, kidney
produce energy. Sugar in the blood- diabetes, 90 to 95 percent have this disease, and even amputation.
stream stimulates particular cells, type. Type 2 has been more common Biotech Possibilities
called beta cells, to produce insulin, among people over 50, but is now Researchers in Chicago believe the
which increases the flow of sugar occurring more often in younger people. scientific community knows enough
from the bloodstream to muscles and Obesity and lack of exercise are major now to treat most diabetes patients
other cells to be used as fuel. Insulin risk factors for this type of diabetes. with therapies that involve changing
also tells the liver to take sugar out of Genetic factors may also play a role. cells themselves, cell-based therapy.
the bloodstream to store for later use. Diabetes can be controlled, but They have formed an international
When sugar levels fall, insulin levels even well-controlled diabetes has project focused on a cure for diabetes
fall and levels of something called consequences. Diabetes affects blood in five years.

Factoid Making Transplants Easier


About 18.2 million Americans, or 6.3 percent of A current but very difficult treatment for diabetes is to transplant a pancreas or its beta cells. Beta cells are
the population, had diabetes in 2002, and the part of the endocrine system and produce insulin. The transplant attempts to replace cells destroyed by the
numbers are rising. Lifestyle patterns you’re immune system. The beta cells can sometimes be injected so they lodge in the liver and produce insulin. But
setting now, as well as genetics, may lead it is difficult to keep the immune system from continuing to destroy the new beta cells, too. In April 2005 for
to or lower the risk you’ll get diabetes. the first time doctors transplanted beta cells from a live donor, a mother to her daughter. Biotechnologists are
developing immunosuppressive drugs to prevent the body from destroying its own beta cells. Gene therapy
genetically modifies beta cells before transplantation to protect them from the immune system. – L.V.
6 Biotechnology and OBESITY
Cell-based therapies being researched include manipu- engineering principles to sensors for administering insulin
lating different kinds of cells to produce insulin. This is pos- or monitoring blood sugar levels.
sible because every cell has the same genetic information Bioengineering is also applied to treating complications
as all other cells; each cell “turns on” a different part from the disease such as blindness. Tiny electrode arrays
according to the kind of cell it is. Currently, advanced med- on a thin sheet of silicon make artificial retinas for diabet-
ical treatments can sometimes transplant insulin-producing ics who are blind.
cells into the body, but many of these cells die or are reject- People working in biotechnology are among those
ed. Other gene therapy includes modifying these cells trying to prevent and treat diabetes, a disease that is
before transplantation so fewer die. an increasing concern as more people get
In type 1 diabetes, the immune system destroys many too heavy. —Linda Voss
components of the insulin-producing beta cells in the
pancreas. An arm of biotechnology called immunogenetics Insulin Production in a Beta Cell in
concentrates on interfering with the processes that destroy the Pancreas. Mitochondria
these cells. Genetic studies are testing members of families (which provide cells with ener-
with diabetes for genes that increase susceptibility or that gy) are green, and the nucle-
us is purple. The folded
protect against diabetes. This type of screening led to the
membrane below the
discovery of insulin-producing cells in the thymus, where nucleus is the endo-
insulin might be used to help train or screen maturing plasmic reticulum,
immune system cells to recognize “self” versus “other,” which divides the
a critical area of malfunction in autoimmune diseases. cell into compart-
These cells have also, unexpectedly, been found in fat ments. Insulin
and bone marrow cells. made in the cell
is packaged in
In other areas of biotech, molecular biologists are secretory gran-
studying how to interfere with the signaling proteins on ules (blue balls in
islet cell surfaces that make them susceptible to attack pink saucers).
by the immune system. These migrate
In bioinformatics, researchers are using computers through the cell and
to manipulate complex genomic information to model a are secreted directly
into a blood
non-obese diabetic mouse in researching type 1 diabetes.
capillary (bottom, con-
Researchers in biotherapeutics are developing such taining red blood cells).
treatments as
● antibodies that protect insulin-producing cells from
immune system attack;
● drugs that stop the immune system from destroying
cells or make cells more receptive to insulin;
● a new drug modeled on the saliva of a Gila monster that
stimulates insulin production.
Biotechnologists have isolated the active compounds in
plants that help the body process glucose, a type of sugar.
Drug makers are even developing insulin powder that peo-
ple would inhale rather than inject. Bioengineering applies

JOHN BAVOSI/SCIENCE PHOTO LIBRARY

Cell Biology of Insulin Response

? Insulin

Glucose
?
Insulin receptor

Closed glucose transporter


?
Open glucose transporter

Normal Cell Type 1 Diabetes Cell Type 2 Diabetes Cell


This is a normal cell. Insulin is present and In type 1 diabetes, insulin is not produced; In type 2 diabetes, insulin is present, but the signal for proper glucose uptake
is taken into the cell to facilitate proper so, there is nothing to signal the cells to and metabolism is lost. The problem could be in the insulin itself or in any one of
glucose uptake and metabolism. take in glucose and metabolize it. the proteins involved in glucose uptake and metabolism.
Your World 7
The roads to controlling

People come in all weights and sizes. Some eat but never gain a pound and others
seem to gain weight by looking at a piece of pizza. So what causes some people to be
overweight?
Researchers are looking in many directions—at brain chemicals that make us hungry
or crave food, at gut chemicals that regulate digestion or feelings of fullness, at ways to
make our bodies burn more fat as energy, or how to prevent the body from absorbing fat.
Most available weight-loss medications suppress appetite by altering chemical
processes in the brain to block feelings of hunger. One prevents the stomach and small
intestine from absorbing some of the fats eaten. Unfortunately, these medications are lim-
ited to very overweight or obese people; some carry the risk of addiction or other
unhealthy side effects or diarrhea, flatulence, and other intestinal
problems; and all but one are meant for only short-
term use.
The quest for new anti-obesity drugs marches
on. Scientists developed a drug, now in late-stage
testing, to block the action of certain brain cell
molecules—cannabinoid receptors—that cause
people to crave food. Overweight people who
took this cannabinoid-1 (CB-1) receptor
antagonist during clinical trials lost more
weight than people not taking it. The drug
may be available in 2006.
Another compound in late-stage test-
ing is ciliary neurotropic
factor (CNTF). This
genetically engineered
version of a human

8 Biotechnology and OBESITY

PHOTO: STEVE GSCHMEISSNER/SCIENCE PHOTO LIBRARY


protein blocks hunger signals in the hypothalamus area of the Investigators are also looking at fat—how we absorb
brain, but it causes some people to develop antibodies it from foods, how we burn it as energy, and how fat cell
that fight the drug’s effect. In a year- receptors work—to try to alter how fat affects weight
long study of overweight people, 259 gain. Biotech scientists are even experimenting with
injecting the drug daily did not form reactivating parts of the human growth hormone
antibodies and lost about 12 pounds, molecule associated with burning fat.
another 720 people developed anti- While studies continue in people, laboratory scientists
bodies and lost about 6 pounds, and study genes associated with obesity and fat cells in mice to
304 people injecting a “dummy” com- try to understand how genes and fat cells work in people.
pound—a placebo—lost 4.5 pounds. One thing is sure: healthy eating habits and regular
Antibody formation will likely limit the exercise control weight gain. Only continuing research
drug’s effectiveness in many people. will identify the most beneficial medications to help
Many compounds are undergoing people who cannot control their weight through diet
early- to midstage testing in people. and exercise. —Joene Hendry
Many alter hormone activities in the
brain or the stomach and intestine;
some block hunger pangs; and oth- Eating Disorders
ers make us feel full after eating a
Obsessing about weight may cause bad
small meal or make people feel full
habits such as eating too little and exercis-
longer to limit snacking. One vaccine
ing too much (anorexia nervosa), or throw-
encourages the body to produce antibodies
ing up after meals (bulemia). Doctors treat
that attach to the hormone ghrelin traveling from
eating disorders by changing how patients
the gut to the brain to signal hunger. Researchers believe
look at themselves, fixing their eating
anti-ghrelin antibodies limit or prevent ghrelin’s hunger signals
habits, prescribing antidepressants, or
from working in the brain.
some combination. Biotechnology scien-
Also being studied is an extract from an African succulent
tists are investigating other treatments for
plant, hoodia gordonii. Only large fleshy pieces of the plant—not
eating disorder.
the powdered form commonly sold on TV or in health food
Many hormones affect appetite and
stores as an appetite suppressant—block hunger. Since the
weight. Scientists wonder why anorexia
plant is rare, a botanical pharmaceutical company is prop-
patients have higher levels of leptin, lower
agating and growing hoodia in
levels of ghrelin, and become resistant to
large test plantations so
growth hormone. It is unclear what is
enough plant extract is avail-
cause and what is effect.
able for further study.
Researchers also study if an anti-obe-
sity drug will prevent people with binge-
eating disorder from throwing up after
eating. They’re also looking into how
genes connected with nervousness may
cause some people to be more suscepti-
ble to anorexia nervosa.
—J.H.

Your World 9
M DE-T - RDER D ETS
what she will eat for the rest of her typically be weaned from their
How is biotech life. mothers’ milk. Now, a test can tell us
addressing the Before that day arrives, scientists which people will get sick—without
have a lot of work to do to discover making them drink any milk.
“diet” part of all the genes that might be relevant Other traits, such as how individ-
to a person’s diet. Some of these uals respond to fat and cholesterol
living healthfully? traits we have known about since in their diets, have only recently
Any two humans, no matter how long before genetic tests were been linked to specific genes. Heart
far removed geographically, have disease is the biggest killer in the
about 99.9 percent of their DNA in United States, so any advance that
common. This close relatedness is can help us understand why some
what makes us a single species—a individuals can tolerate a given
species, after all, is just a group of amount of fat in their diet while oth-
Nutrigenomics; ers cannot could help save millions
organisms that can reproduce with
The study of of lives.
one another. Yet, the tiny fraction of
how nutrients Scientists will also need to gain a
our DNA that varies from one person
and genes better understanding of the recipro-
to the next can determine a lot—
interact. cal relationship between food and
everything from physical features
such as height and skin color to less genes—that is, not just how genes
obvious characteristics, such as affect what we should eat, but also
how well each body uses the vast how what we eat affects our genes.
array of substances present in food While good examples of this phe-
for energy. nomenon are hard to come by in
The science of sorting out what invented. For example, nine out of humans, studies in mice suggest
each of us should and should not 10 adult Asian Americans will get that mothers who don’t consume
eat is known as nutrigenomics, or sick if they drink milk. That’s enough nutrients can change the
nutritional genomics. This kind of because members of this population methylation of their own DNA.
personalized nutrition seeks to pro- lose their ability to produce lactase, Methylation is a chemical change
vide a molecular understanding for the enzyme that that adds a methyl group (a carbon
how what we eat (i.e., nutrition) digests and three hydrogen atoms) to a spe-
affects health by changing an lactose, a cific place on your DNA, and methy-
individual’s genes, what the sugar pres- lation is one of the ways our bodies
genes produce (express), or ent in milk, turn on and off genes during the
both. Scientists who do soon after course of our lifetime. Intriguingly,
research in this field have dis- they reach the these changes may even
covered, perhaps not surprising- age at which be passed on to a
ly, that there is no one-size-fits-all they would mouse’s offspring.
diet. While the field is still A handful of com-
young, it’s possible panies have already
that some day a begun offering
test will screen genetic
a child for hun- screens for
dreds of possible gene variants
gene variants and known to be
that this information linked to everything
will help her choose from heart disease to

10 Biotechnology and OBESITY


diabetes. Not everyone is happy with
the testing, however. Objections range
from privacy concerns—if a health
insurance company found out you had
a predisposition to heart disease,
would it be less likely to insure you?—to
concerns about the ultimate relevance
of these tests to a person’s health.
Concerns about the importance
of the “disorders” uncovered by most
nutrigenic tests are perhaps the biggest
barrier to progress in this field. As some
academics and watchdog groups have
pointed out, except for a few relatively
rare disorders, most of what nutrigenic
tests tell us are things we should
already know: that regardless of our
individual susceptibilities, the key to
good health is to avoid smoking, eat
a healthy diet, and exercise regularly.
(Many scientists are skeptical about
supplements being sold, too.)
On the other hand, it’s possible that Obesity Growth Spurt
knowing precisely how changes in diet Data are based on two national studies done in Canada (Tremblay & Wilms, 2000).
can prevent disease will encourage us
to recognize, as Hippocrates put it
nearly 2,500 years ago, that we should Learn More
“let food be our medicine, and medi- “Diet & Genes,” Newsweek, January 10, 2005,
cine be our food.” http://www.sciona.com/industry-news-
events/2005/01/newsweek-diet-genes.html
—Christopher Mims
University of California–Davis,
http://nutrigenomics.

Bioengineering Healthier Food


Fish are rich in omega-3 fatty acids, which are increasingly
recognized as a “superfood” that appears to boost everything from
heart health to mood. Unfortunately,
many of the fish rich in omega-3s
are either quickly disappearing from
the oceans or contain worrisome
levels of mercury, or both. Enter a
Harvard research team led by Dr.
Jing Kang, who has figured out how to use genetic engi-
neering to insert a gene for an enzyme found in C. elegans into
mammalian cells that lack the enzyme to convert omega-6 fatty
acids into omega-3 fatty acids. They have created transgenic mice C. elegans. The Caenorhabditis
expressing the omega-3 enzyme (desaturase). The technique might elegans nematode worm is a
some day be applied to livestock, yielding heart- soil-dwelling bisexual organism.
One of its enzymes can help
healthy steaks and, perhaps more importantly,
mammals produce healthful
adding to the handful of natural sources of omega-3 fatty acids.
this valuable nutrient. —C.M.
SINCLAIR STAMMERS/SCIENCE PHOTO LIBRARY

Your World 11
You can’t watch television these days without seeing news about childhood or adult obesi-
ty. Schools throughout the nation are banning junk foods and sodas high in sugar to rein-
force good health and diet practices. The federal government even has sent researchers
to West Virginia to try to understand why its residents have such a high obesity rate.
Nutritionists and doctors continue to champion better nutrition and more exer-
cise for today’s overweight youth and adults. To help in the struggle to lose
excess weight, the biotechnology and pharmaceutical industries also are
busy developing anti-obesity drugs. The stated goal is to avert the adverse
health consequences, such as heart disease and diabetes, that can
occur with extra weight and poor diet.
But when might it be appropriate to use diet and exercise only
or anti-obesity drugs that are available—or both—in people?
And in a culture fixated on the pursuit of being as skinny as
models and TV stars, some people might use drugs to
meet artificial standards of weight rather than health
goals. Here are some cases to consider as you think
about which interventions might best be used.

John G. is 7 years old and has Prader-


Willi syndrome, a condition that causes him
to be overweight. Characterized by compulsive
eating and an obsession with food, the disorder often
begins before age 6. Problems in the hypothalamus, part of
the brain that regulates appetite and satiety, are believed to cause
the disease. His parents must strictly supervise his eating and
even lock the kitchen and food storage areas at home. Weekly,
John sees a child psychiatrist to help him cope.

What if a drug could be developed that would curb


John’s appetite, allowing him to live a life not
subject to continual food monitoring by his
parents and other adults? Should he get it?

12 Biotechnology and OBESITY


Mary H. is 11 years old and 25 pounds overweight. Her mother,
father, and brother also are overweight. No one in the family eats
healthfully. The parents give their children money for breakfast at
fast-food restaurants. At school, the fare also is high in carbohydrates and fat. For dinner,
the family often orders pizza. Family time is spent watching television eating! The cup-
boards are filled with potato chips and cookies. They eat very few fruits or vegetables.
Mary, near puberty, has decided she wants to lose weight and
hopes to help her family do so, too. She has tried to eat salads and
exercise, but it is hard for her to keep weight off when others in her
family have not changed their eating styles.
What if Mary can
convince her family to
see a physician so they
all can start a prescrip-
tion regimen for a new
anti-obesity drug? Should
they all start on a drug
or should a diet and
exercise program be
Frank W. is 14 years old. He is athletic, hand-
the goal?
some, and a good student. Unlike others at his
school, he understands proper nutrition and
physical exercise in maintaining his weight. Most
of the time, he is careful about what he eats and
works out to keep in shape. On some weekends,
though, Frank likes to indulge in eating frenzies,
wolfing down cheeseburgers, fries, ice cream,
and candy. By Monday, he often has gained some
weight. To lose the extra pounds, during the rest
of the week, he cuts back heavily on calories,
sometimes to the point of not eating enough
food and feeling faint.

Frank finds out a new anti-obesity drug might


make it easier for him to quickly lose the extra
weight he gains on those overindulgent weekends.
He tells his parents he wants to see a doctor to get a
prescription for the medication because he is afraid
he will get fat. Should the doctor give it to him?
—Robin Eisner

Your World 13
ROCKEFELLER UNIVERSITY
LEARNING FROM FAT MICE
Jeffrey M. Friedman, M.D., Ph.D.
Marilyn M. Simpson
Professor and Investigator A mutation makes these mice obese. After 4 1/2 weeks, the
Howard Hughes Medical Institute mouse (R) that received daily injections of leptin weighed 35
grams while the untreated mouse (L) weighed about 67 grams.
The Rockefeller University (Normal mice weigh about 24 grams.)

The mice in Jeffrey Friedman’s laboratory aren’t captured my imagination,” he says. “And I enjoyed
your ordinary rodents. They’re superfat, three times science so much I decided to go back to school and
larger and five times fattier than other mice. And it’s get a Ph.D.” By 1986, he had a doctorate in molecu-
a good thing they’re big, because Friedman’s career lar biology and his own lab at Rockefeller University.
rests upon their shoulders. Thanks to his discoveries, he now has the chance
Friedman attracted worldwide attention in 1994 to help more people than any one physician ever
when he figured out why this strain of mouse is so could.
fat. By analyzing their DNA, he discovered that these “There’s a popular view that obesity results from
mice lack a gene responsible for encoding a hormone a lack of willpower or [from] fast food,” Friedman
that normally zips through the bloodstream and tells says. “While these things are clearly relevant, the evi-
the brain, “Stop eating.” Friedman later found that dence shows that obesity is highly genetic—almost
another strain of obese mice lack the receptor in as inheritable as height.” The discovery of a powerful
the brain designed to receive the “I’m full” message. biological system operating under the conscious
As a kid in suburban Long Island, Friedman wasn’t mind’s radar screen could help destigmatize obesity,
thinking, “I want to be a fat-mouse specialist when he says.
I grow up!” He wanted to become a doctor, like most His discoveries could also lead to an obesity
of the scientifically minded kids in his neighborhood. treatment. Mice injected with the missing hormone
So he did. After graduating from high school at 16, he —called leptin—lose weight like mad. They also
earned a medical degree at 22. But while Friedman recover from diabetes. These findings have sent the
enjoyed caring for patients, he sensed a medical biotechnology industry scrambling to come up with
career would leave him intellectually hungry. an obesity drug that would do the same for people.
He spent the year 1980 working in a research lab, In the meantime, Friedman has extended his own
where he first encountered the obese mice. “They research to humans. He’s made three visits to a far
Pacific island called Kosrae to study human obesity.
Adapting the techniques he once used on mice, he
is exploring the link between differences in DNA and
differences in weight among these isolated islanders.
On a typical day, however, Friedman is in his New
York lab. He spends most of his time writing and
talking with people. Rather than conducting experi-
ments himself, he oversees a lab consisting of the
mice, 15 scientists, and a constantly rotating cast
©2004 PAUL FETTERS FOR HHMI

of high school, college, and postgraduate students.


Will Friedman’s seven-year-old twins follow in his
footsteps? He says it’s too early to tell, although the
girls enjoy visiting the mice. “What I do has some
attraction for them,” he says with a laugh, “but it’s
partly because they like the fact I’m boss.”
—Rebecca A. Clay

14 Biotechnology and OBESITY


Leptin to the Rescue? Research a Cure
With the necessary kit, you can explore what it is like to
To complete this activity, a “Green Fluorescent be a researcher producing long-lasting leptin. Hydrophobic
Protein (GFP) Purification Kit” needs to be interaction column chromatography (HIC), a technique used
in biotechnology to separate and purify proteins, will enable
ALFRED PASIEKA/SCIENCE PHOTO LIBRARY

ordered.* A UV lamp with long wavelength


is needed to see the green fluorescence. you to isolate a simulated modified leptin from an extract of
A system of genes, proteins, and bacterial proteins. HIC takes advantage of the fact that some
neurotransmitters controls how our proteins are more hydrophobic (“water hating”) than others;
bodies store fat—and this regulates they bind to the chromatography gel and thus wash out of
what we weigh. This system tells our the HIC column less easily. As you lower the salt content of
brains not only when we should eat, your solution, you will observe that the simulated modified
but also when we should stop eating. leptin, which is more hydrophobic than the other bacterial
One of the proteins responsible is called proteins in your extract, remains in the HIC column longer
leptin. Produced in our fat cells, leptin helps than the less hydrophobic proteins.
to send signals to the brain that we are full. ■ First, your teacher will help you grow bacteria containing
Some researchers have hypothesized that leptin, a simulated modified leptin, which has been tagged with a
discovered in 1997, may help us treat obesity. green fluorescent marker to make it easier for you to see.
Because obese mice injected with leptin lose weight, this protein looked Now you are ready to follow these steps:
like an easy treatment for obesity. However, scientists discovered that leptin ■ In a microtube, centrifuge the enzyme-digested bacteria
made in the human body does not last very long. It would take leptin injections containing the simulated modified leptin for 10 minutes.
or leptin pills every hour to produce in humans the same results as in mice, ■ While centrifuging, prepare your HIC column by adding 2
making it very expensive and inconvenient! mL of equilibration buffer. Drain the buffer until 1 mL is
To solve the problem, scientists are investigating the idea of genetically left above the top of the gel matrix.
modifying leptin so that it will last many hours, or even days, in the human ■ After centrifuging, view the tube with UV light and note
body. This involves genetically engineering bacteria to produce a new kind your observations on your data sheet.
of leptin with amino acid differences that slow its breakdown in our bodies.
■ Transfer 250 uL of supernatant to a new microtube and
label it “Modified Leptin.” Transfer 250 uL of binding
A Question about Leptin buffer to the “Modified Leptin” microtube and then mix.
Researchers have found that some obese individuals have high levels of leptin,
■ Label three collection tubes 1, 2, and 3. Place the HIC
while some other obese individuals have low levels of leptin. Based on what you
column on top of Tube 1. In this tube, collect the 1 mL of
know about this protein, how do you think both of these situations could result in
buffer that is on top of the gel. Examine the column using
obesity? An Internet or literature search can help you find additional answers.
UV light and note your observations.
■ Take 250 uL of the solution from the tube labeled “Modified
Leptin” and load it on the top of the column. Let this
solution drip into Tube 1. Examine the column using
UV light and note your observations.
■ Transfer the column to Tube 2. Add 250 uL of wash buffer
to the column and let it flow through the column into Tube
2. Examine with UV light and note observations.
■ Transfer the column to Tube 3. Add 750 uL of TE (modified
leptin elution) buffer to the column. Let the solution pass
through the column and collect in Tube 3. Examine with
UV light and note your observations.
■ On your data sheet, note any differences in color among
the three tubes and column at each of the three. Report
whether you were successful in isolating your simulated
modified leptin from the bacterial extract.

Investigate Leptin
■ Design a study to determine if a genetically modified,
long-lasting leptin could help obese individuals.
■ What is your hypothesis?
■ What control and experimental groups would you use to
Adapted from the DESTINY Traveling Science Learning Program’s module Weigh to Go! Discovering the test your hypothesis?
Genetics and Biochemistry of Weight. ■ What variables would you need to control?
*See Teacher’s Guide online at <www.biotechinstitute.org>. ■ What experimental results would you predict?
Your World 15
Resources
Eating Disorders
NIMH, “Eating Disorders: Facts about Eating Disorders and the Search
for Solutions,”
<http://www.nimh.nih.gov/publicat/eatingdisorders.cfm>.
American Medical Association, “News from the AMA: Anti-obesity Drug
May Help Treat Binge Eating Disorder,” November 11, 2003,
<http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZB8
TBAWMD&sub_cat=0>.
BioPortfolio, BioNews, “Genetic Interactions May Establish Susceptibili-
ty to Anorexia Nervosa,” May 5, 2005,
<http://www.bioportfolio.co.uk/cgi-bin/dialogserver.exe?CMD=hit.display
Mdoc&ID=54746&HITNO=0&MSIZE=23&LANGUAGE=en&FILE=doc.NEW
SFEED&SAVEQUERY00=Eating%20Disorders&SAVEPROP00=L%3den&S
AVEDB=news_trial&SAVEORGANISE_CODED=R:date&R=54746&THISHR
EF=file:/D:/newsedge/newsedge_06_05_2005/nitf/St_Nitf_Genetic_inter-
actions_may_estab_c0506644.3wh.xml&THEHOST=>.
Harvard Eating Disorders Clinic, HEDC Research,
<http://www.hedc.org/>.
The Roads to Controlling Obesity
Stephanie Saul, “Drug Makers Race to Cash In on Nation’s Fight Against
Fat,” New York Times, April 3, 2005.
Nutrigenomics
University of California–Davis,
<http://nutrigenomics.ucdavis.edu/>.
“Examining the Ethical Issues of Nutrigenomics,”
<http://www.mydna.com/genes/nutrigen/library/ethicalnut.html>.
“Nutrigenomics: The Next Wave in Nutrition Research,”
<http://www.nutraceuticalsworld.com/marapr001.htm>.
Diabetes
REMEMBER TO ENTER!
Students: Be sure to enter the 2006 BioDreaming Poster Competition. Top prize Centers for Disease Control and Prevention, “Genetics and Genomics,”
in each age category is $500. To learn how to enter, visit our Web site at <http://www.cdc.gov/node.do/id/0900f3ec8000e2b5>.
http://biotechinstitute.org/programs/biodreaming.html. Chang, Alicia, “New Drug Shows Promise in Type 1 Diabetes,” Associated
Teachers: Be sure to apply for our 2006 National Biotechnology Teacher-Leader Press, June 22, 2005, <http://abcnews.go.com/
professional development program in Chicago, April 6 to 9. All expenses with Health/wireStory?id=873209&CMP=OTC-RSSFeeds0312>.
the exception of travel are covered. Visit “Diabetes and Driving,” dLife, Adapted from United States Department
http://biotechinstitute.org/programs/t_leader_program.html of Transportation, Publication 809-604, <http://www.dlife.com>.
for application information. Diabetes Research Institute,
<http://www.drinet.org/html/the_diabetes_research_institut.htm>.
“Genetics of Type II Diabetes,” New Mexico State University,
THE BIOTECHNOLOGY INSTITUTE WOULD LIKE TO THANK ITS 2005 <http://darwin.nmsu.edu/~molbio/diabetes/disease.html>.
CORPORATE DONORS AND INDIVIDUAL DONORS GIVING $5,000 OR MORE. JAMA 292 (2004): 927-34.
Abgenix Chiron Foundation Ligand Pharmaceuticals, Inc. “Manipulating Anti-IGRP Autoimmunity May Prevent Diabetes,”
Alfa Laval Biokinetics Inc. Connetics Corporation MdBio Diabetes Today, June 3, 2005.
Amgen, Inc. CV Therapeutics, Inc. Merck Company Foundation
Baxter Biosciences, Inc. Department of Energy Monsanto Fund
MitoChroma® Research, Inc., <http://www.mitochroma.com/>.
Biogen Idec Foundation
Biotechnology Industry
Organization
Discovery Labs, Inc.
Ernst & Young LLP
Exelixis Inc.
Nektar Therapeutics
NIAID
Ortho Biotech, Inc.
YOUR WORLD visit us online
Biotechnology Institute Genencor International, Inc. Pfizer Foundation www.biotechinstitute.org/yourworld.html
Board of Directors Genzyme Corporation Protein Design Labs, Inc.
Burrill & Company Gilead Sciences Inc. Sangamo BioSciences, Inc. Online you’ll find
Cell Genesys Inc. Hoffman-LaRoche Inc. sanofi-aventis
Centocor, Inc. Invitrogen Serono ❚ Teacher’s guide ❚ Links
Cephalon Lehman Brothers Wyeth ❚ Activity supplement: student and teacher procedures
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