When a Gene Makes You Smell Like a Fish ...
and Other
Amazing Tales about the Genes in Your Body
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OXPORD
UNIVERSITY PRESS
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Copyright © 2006 by Lisa Seachrist Chiu
First published by Oxford University Press, Inc., 2006
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www.oup.com
First issued as an Oxford University Press paperback, 2007
Oxford is a registered trademark of Oxford University Press
All rights reserved. No part of this publication may be reproduced,
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Library of Congress Cataloging-in-Publication Data
Chiu, Lisa Seachrist.
When a gene makes you smell like a fish
and other tales about the genes in your body
Lisa Seachrist Chiu;
Illustrations by Judith A. Seachrist.
p. cm. Includes bibliographical references and index.
ISBN-13: 978-0-19-516994-2
1. Human genetics—Popular works.
2. Human genetics—Anecdotes.
I. Seachrist, Judith A.
II. Title.
QH431.C4742006
599.93'5—dc22 2005031803
ISBN 978-0-19-532706-9
35798642
Printed in the United States of America
For Dan and Any*
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Contents
Acknowledgments ix
Introduction \
When a Gene Makes You Smell Like a Fish 4
chapter One
It Takes Two to Tango 12
The First Gene 16
Phenylketonuria and the First Genetic Test 21
Maple Syrup Urine 27
The Tangier Island Gene 34
The Celtic Curse 40
Metallic Madness 45
chapter TWO
Just One Bad Apple . . . 49
The Long Stretch Gene 50
The Dracula Gene 56
The Expandable Gene 60
chapter Three
You Can Blame It on Mom 66
The Gene That Launched a Revolution 67
The Fragile X 74
The Werewolf Gene 79
The Cue Ball Gene 81
viii Contents
chapter Four
our
Leaving an Imprint 84
Whither Mom or Dad Gene 86
The Calico Cat Gene 94
When a Gene Won't Silence 101
chapter Five
Just a Little Piece of the Puzzle 109
Speaking with a "Forked Tongue" 110
The Cheeseburger Gene 115
The Bitter Gene, or The Battle over Broccoli 119
The Schwarzenegger Gene: From Mighty Mice
to Hulking Human 125
A Performance Gene 130
An Aging Gene 134
chapter Six
In the Beginning. . . 140
The Cut-and-Paste Genes 140
Jomon Genes 145
Survivors' Benefit 151
The Pregnancy Genes 156
The "Got Milk?" Gme 164
Innate Sensing Genes 167
The Sidedness Genes 172
Epilogue: Snippets of Information
Reveal the Whole? 179
Appendix: A Genetics Primer 184
References 192
Index 211
Acknowledgments
This project would have been impossible without the gen-
erous help and inspiration of a host of friends, family,
colleagues, and professionals. My gratitude to those who en-
couraged, cajoled, aided, and abetted me far outweighs the
simple mention that I make of it here.
I owe an eternal debt of gratitude to my agent Jeanne Hanson
for getting this project off the ground and to my friend and
colleague John Travis for having the confidence in my abili-
ties to realize this book. My partner-in-crime and friend Karen
Foxkvetched over coffee, read manuscripts when needed, and
spurred me to "write like a writer." Good information is the
lifeblood of any undertaking of this size. Wendy Chiu, Harry
Wong, and numerous scientist friends shared their knowledge,
offered encouragement, and patiently granted me access to
their extensive libraries whenever I needed them. Alice Chiu
and Kristen Truitt provided critical advice, equipment, and the
know-how that I needed to create suitable graphics for this
book. I also must thank Andrea Doughty for taking my pan-
icked phone calls and providing last minute translations. Judith
Hall provided a scientific review of the manuscript. I want to
thank my editor Peter Prescott for his expertise, cheerleading,
gentle pressure, and basically just putting up with me during
this process.
My brother Mike Seachrist, my grandmother Mary Perrin,
and my in-laws Ray and Jane Chiu gave me their encourage-
ment and support throughout this process. My father, Michael
Seachrist, offered a calm confidence in my abilities that proved
x Acknowledgments
a priceless gift. My husband, Daniel Chiu, provided loving sup-
port and confidence every step of the way If I can be half as
supportive to him as he has been to me, I will have achieved a
great good. Finally, I must thank my illustrator and mother,
Judith Seachrist, without whom this book would never have
been completed. Aside from the beautiful watercolors she
painted for the illustrations contained in the following chap-
ters, she gave me months of her life just to make sure this book
could be born. It's a gift and sacrifice that I will never be able to
repay My only hope is that one day I can pay this generous gift
forward to my own daughter, Anya.
When a Gene Makes You
Smell Like a Fish
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Introduction
i was by all accounts a strange child, but for as long as I can
remember, I've been fascinated with inheritance. As a five-
year-old, I badgered my mother to explain to me why the twins
down the street looked exactly alike, but the set two blocks over
looked so different I couldn't believe they were even sisters,
much less twin sisters. Shortly thereafter, my poor mother
received yet another demand for explanations as I peppered
her with questions asking why my brother had blue eyes and I
had brown eyes. At the time, I figured that I had brown eyes
like my mom because I was a girl. Therefore, my brother—a
boy obviously—sported my father's striking cobalt eyes. That
explanation made perfect sense to my elementary-school mind. I
give my mother, a theater major in college, enormous credit be-
cause she actually tried to explain to me that my formulation was
incorrect and that "genes" somehow determined whether I had
blue eyes or brown eyes. She even tried to describe that blue eyes
were something called recessive, and two blue-eyed parents could
produce only blue-eyed children. That proved a doomed effort
in part because the concept is beyond the average six-year-old.
My fascination with genetics blossomed, and one day in the
third grade I found myself an eager participant in Emily
Fontana's tongue-rolling experiment during recess. Emily said
that if I could roll my tongue, then one of my parents could too
and that I had inherited the ability from whichever parent that
was. I knew I could roll my tongue, so I fidgeted all afternoon
agonizing as the clock crept closer and closer to three o'clock.
As soon as the bell rang, I raced out of the classroom, cutting
2 When a Gene Makes You Smell Like a Fish
through all the verboten backyards just to shave five minutes
off the walk home. I made it home in record time only to dis-
cover that both my parents could roll their tongues.
Robbed of my chance to pinpoint the source of at least one of
the traits I possessed, I figured it would be only a short matter of
time until I had another chance. With my child's view of the
world, I believed our genes told us where we came from, who
we were, and what we would become. At age eight I was a ge-
netic Calvinist clinging to the predestination written into our
genes. Such black-and-white thinking is characteristic of child-
hood, after all. I'm not sure at what point in high school or college
I began to understand and appreciate the nuance in our biological
systems. I do know that by the time I first witnessed bacteria adapt
to the environment (a food source lacking a critical nutrient), I was
captivated by what our genes could and could not do.
Critical to my appreciation of genetics was the understand-
ing that by and large genes don't actually do anything at all. When
Watson and Crick described the DNA double helix that served
as the body's "heritable" material, they shocked the scientific
community by describing an intertwined molecule that had no
known function rather than a molecule such as a protein that
could actually do things. Indeed, the double helix is just two
long strands of interlaced DNA that serve as the blueprint that
the cellular machinery uses to make the action molecules in the
cells of our bodies. If this bit of information came as a surprise,
I invite you to take a look at the Genetics Primer in the back of
the book. It's never a bad idea to brush off the cobwebs clinging
to the information gleaned from your last biology class. How-
ever, if you can't bear the thought of being schooled, I promise
you that most of the stories contained in this book will still be
well within your grasp.
By the time the Human Genome Project was launched in 1990,
the stories of many genes were known. But the effort to sequence
the entire genome enriched that understanding and unveiled more
than a few biological surprises. Still, as Francis Collins repeat-
edly stressed, the completion of the Human Genome Project in
2003 is just the beginning of our understanding of genetics and
Introduction 3
Genes are housed on the intertwined strands of DNA that make up the
double helix.
biology, and indeed he was correct. Having the sequence of the
entire genome hasn't suddenly cured diseases or discovered the
gene for road rage. It has, however, provided the scientific com-
munity with an invaluable tool to explore the ways our genes
interplay with each other and the environment.
So, read these stories not as examples of immutable truth
and predestination, but as the present understanding of these
genes. Who knows what future studies will unearth? The ex-
citement comes with furthering our understanding and pin-
ning down each new detail only to discover a new wrinkle in
how our bodies use the intricate information stored in our genes.
With the human genome laid bare, scientists are rapidly dis-
covering how the text of the genome is read in concert with
things like diet, health behaviors, experiences, and other genes.
With that knowledge, we gain better understanding about our
similarities and differences as human beings. The short tales in
this book are simply entertaining and thought-provoking snip-
pets of the scientific discoveries driving the "Age of Biology."
Just to set the record straight, my mother had no chance of
explaining to me how blue eyes are recessive to brown eyes. Eye
color is governed by several genes, and is, therefore, neither a
recessive nor a dominant trait. Oh, and I did pinpoint which par-
ent endowed me with my tongue-rolling ability. Neither one.
Rolling your tongue is an acquired skill not a genetic one.
When a Gene Makes
You Smell Like a Fish
N ew 'Vbrker Sandy Gordon knew something was amiss. It
started with whispers and comments at work. Co-workers
began stopping near her desk loudly asking, "What's that smell?"
or "Who needs a shower?" And, she thought, yeah what is that
smell?
And then there was that foul odor in her apartment that so
annoyed her she had the building superintendent in to fix her
bathroom only to find it still stank after the repairs were com-
plete. When her nieces and nephews told her, "Aunt Sandy, you
didn't brush today. Your breath stinks," she thought, perhaps, it
was something she had eaten.
The awful truth came when a friend and co-worker suggested,
no insisted, that they have lunch together one day. Instead of a
quick bite to catch up on things, her friend told her that5/ze was
the source of the odor so foul and fishy it was disrupting the
workplace.
"I just started crying in the restaurant," she says. "Here was
the horrific realization that all those comments were about me.
The smell came from me."
Devastated, Gordon went straight home and informed her
company that she would be taking a three-month leave of ab-
sence to deal with her problem. "I am so grateful to my friend
for dealing with it," Gordon says, "She said all the right things.
She told me, I know you are a clean person; I've been to your
house. It is extremely difficult to be truthful and she was."
When a Gene Makes You Smell Like a Fish 5
In her early thirties, Gordon knew she hadn't been feeling
particularly well. So she figured she would work with her doc-
tors and beat whatever was making her smell. Eighteen doctors
later and $28,000 out of pocket, Gordon discovered her odor
condition wasn't a simple case of taking some medicine and
being done with it. She learned she had a nonfatal but incurable
genetic disorder: trimethylaminuria (TMAU) also known as fish
odor syndrome.
As a result of genetic mutations, Gordon's body fails to pro-
duce an important liver enzyme that breaks down a smelly sub-
stance called trimethylamine (TMA), an ordinary by-product of
digesting foods high in protein. For Gordon and other sufferers,
this enzyme simply doesn't work and, depending on what they
eat, the odor emanating from them can be barely perceptible to
slightly garbagelike to the overwhelming stench of rotting fish.
Body odor isn't socially acceptable, so it's understandable that
many people suffering from TMAU find themselves depressed,
un- or-underemployed, isolated, and lonely. Gordon got a first-
hand glimpse of the isolation when colleagues started making
their "What stinks?" comments. She even had a colleague who
complained to her supervisor about the odor. To the supervisor's
credit, the complaining colleague was informed that only when
said colleague was as productive as Gordon would the employer
tolerate complaints about Gordon. Surprisingly, Gordon con-
siders herself lucky. "I've always been a strong person and had a
family that taught me to know who I was and to stand up for
myself."
The first clinical case of TMAU was described in 1970 in the
medical journal The Lancet, but literary references go back more
than a thousand years. Shakespeare's Tempest describes the out-
cast Caliban, "He smells like a fish; a very ancient and fish-like
smell . . . " Hindu folklore mentions in the epic Mahabharata
(compiled around 400 AD) a maiden who "grew to be comely
and fair, but a fishy odor ever clung to her."
The biochemical cause for the stink is the huge amount of
TMA people with the disorder secrete into their urine, breath,
and sweat. People suffering from TMAU literally walk around
6 When a Gene Makes You Smell Like a Fish
in a cloud of odor—at body temperature, TMA is a gas. Unfor-
tunately, TMA is a part of everyone's life for it is naturally pro-
duced when beneficial bacteria in the human gut breakdown
foods high in choline—an essential building block of proteins
and a vital component for normal fat and carbohydrate metabo-
lism as well as nerve and brain development. Foods like egg yolks,
liver, organ meats, and cruciferous vegetables like broccoli and
cauliflower as well as the emulsifier lecithin all contain large
amounts of choline, which is broken down into TMA. The dif-
ference for people with TMAU is that they lack the enzyme
needed to turn the stinky TMA into a nonodorous molecule.
Scientific and medical literature documents about a hundred
or so cases of TMAU, but the real prevalence of the disease is
hard to know. Researcher's estimates range from 0.1 percent to
1.0 percent of the population worldwide—in the United States
this would mean as many as 250,000 individuals. John Cashman,
director of the Human BioMolecular Research Institute in San
Diego, notes many physicians assume odor is simply a bad case
of halitosis or that the patient may be overly sensitive to odors
or may be suffering from obsessive-compulsive disorder. As a
result, people suffering with TMAU can wait for years to get a
diagnosis.
Since the disorder was first described in the 1970s, physicians
have diagnosed patients with fish odor syndrome on the basis of
measuring excess TMA in their urine after they have eaten a large
amount of choline—a test called a choline challenge. In 1997,
physicians got another tool for confirming the diagnosis of
TMAU: the gene associated with the disorder was identified:
flavin-containing monooxygenase (form 3) or FMO3. This
gene—housed on chromosome 1—is expressed in the liver and
is part of a family of genes encoding proteins responsible for me-
tabolizing and/or detoxifying drugs and molecules that contain
nitrogen, phosphorous, selenium, and sulfur. Cashman and col-
leagues at the Seattle Biomedical Research Institute discovered
specific changes in the FMO3 gene that could interrupt the func-
tion of the enzyme. When FMO3 can't function, people have no
way to turn TMA, which contains a nitrogen atom, into the odor-
less substance called TMA-N-oxide.
