ENTIRE SEQUENCE OF THE HUMAN GENOMEA MOLECULAR MAP WRITTEN
IN CHEMICAL CODE AND TUCKED INSIDE EACH OF OUR TRILLIONS OF CELLSRESIDES
IN A COMPUTER SERVER ON THE THIRD FLOOR OF THE WHITEHEAD BIOMEDICAL
it came to be here, in Emorys Department of Human Genetics,
and what that means for researchers is a story that begins fifty
years ago with James Watson and Francis Crick bursting into
a pub in Cambridge, England, shouting that they had found
the secret of life.
young scientists had discovered the structure of DNA, the double
helix of chromosomes containing the genetic codes that help
determine whether we will be tall or short, have brown eyes
or blue, curly hair or straightperhaps even if we will
be shy or outgoing, or prone to Alzheimers or obesity.
the next five decades, other important genetic discoveries were
made: diseases that resulted from chromosomal abnormalities,
such as Down syndrome; genetic engineering, in which genes are
reshuffled from one species to another; genetically engineered
drugs and vaccines; genetic fingerprinting, which can identify
individuals from a strand of hair or a drop of blood; genetic
testing of embryos.
occasionally decry this burgeoning genetic experimentation,
claiming that scientists and biotech companies are opening a
Pandoras box with unpredictable consequences. But, in
truth, the box already has been opened.
1990, at the urging of Watson himself, Congress funded the Human
Genome Project, an international effort to identify the information
encoded in human DNA. All genes are made of combinations of
four chemicalsadenine, cytosine, guanine, and thymine,
abbreviated A, C, G, and T. The project would determine the
sequences of the genomes three billion letters and store
this information in databases open to public and private researchers.
With this blueprint of genetic instructions in hand, experts
reasoned, scientists would be able to gain insight into evolution,
discover the origins of hereditary diseases, and develop new
June 2000years ahead of schedule and under budgetscientists
released the first rough draft of the genome. President Bill
Clinton called it the most important, most wondrous map
ever produced by mankind.
this same time, various genetics programs at Emory were being
pulled together under one roof, with the intent of coordinating
research and clinical services under the newly christened Department
of Human Genetics.
is a happening place, says Timmie Professor of Human Genetics
Stephen T. Warren, who was named chair of the department in
2001. Our goal is to become one of the top ten departments
in human and mammalian genetics in the country.
just a few years, the genetics department, which is part of
the School of Medicine, has expanded its faculty from five to
twenty-eight and increased federal research funding by 170 percent,
from $2.2 million in 2000 to more than $6 million in 2003. It
houses the editorial offices of a leading specialty journal
in the field, the American Journal of Human Genetics.
department opened a new Center for Medical Genomics with advanced
robotics for DNA extraction and genotyping, an Emory Down Syndrome
Center, and an Emory-Baylor National Fragile
X Centerone of three in the country.
a move that underscored its intent to merge research and practice,
the department incorporated the Division of Medical Genetics
(formerly part of the pediatrics department). This division
provides adult and pediatric genetic disease counseling and
operates three diagnostic labs.
W. Woodruff Professor of Human Genetics David Ledbetter, former
chair of the Department of Human Genetics at the University
of Chicago, was recruited to be chief of the division.
talks a great deal about translational researchfrom
the bench to the bedsidebut almost no one creates
a structure to push that forward, Ledbetter says. Science
and medicine take place in different buildings, in different
cultures, and wait for a miracle to happen. In our department,
weve got it allthe research labs and the diagnostic
labs, the scientists and the clinicians. It expedites the process
tremendously when you can wander down the hall and talk to colleagues
who are on the receiving end of your research.
Genetics Metabolic Center, for example, not only conducts research
into phenylketonuria (PKU), Maple Syrup Urine Disease (MSUD),
and other metabolic disorders, but also has dieticians who design
nutritional plans and offer cooking classes for patients and
their families, a clinic where routine checkups and blood work
can be performed, a retail store with special formula and low-protein
foods, and a summer camp for young women with metabolic disorders.
is a genetic disorder that occurs in one out of 15,000 births
in the United States. When both parents are carriers, there
is a one in four chance their child will have the disorder.
MSUD, whose name is derived from the burnt-sugar smell of the
urine of infants with the disorder, is more rare, occurring
in one in 225,000 births. Without screening and early treatment,
infants with PKU or MSUD will develop mental retardation and
consists of a carefully controlled diet begun during the infants
first days or weeks, which often must be followed for life.
Frequent blood monitoring is necessary.
relationship with these families can begin as soon as their
infants are screened, says Rani H. Singh, assistant professor
and director of the departments nutrition section. We
want to demonstrate how good nutritional management can improve
outcomes and the quality of life for our patients.
3 percent of newborns will have a genetic disease or significant
birth defect, and at least one third of pediatric hospitalizations
are the result of a genetic condition. It is now routine to
screen embryos for genetic disorders before they are implanted
in the mothers womb during in vitro fertilization.
say that in the not-too-distant future it might be possible
to sequence an individuals genome for as little as $1,000,
providing a personal guide for predicting susceptibility to
diseases and choosing the most appropriate treatments.
gain knowledge of ones genetic fate, however, delivers
its own complications. A case in point is Huntingtons
disease, a degenerative neurological disorder that strikes
one in ten thousand and doesnt occur until adulthood.
It results in progressive uncontrolled movements, loss of intellect,
and emotional disturbances, sometimes to the point of madness.
Each child of a parent with Huntingtons has a fifty-fifty
chance of inheriting the gene.
a horrible disease, said Randi Jones, an Emory neuropsychologist
who specializes in Huntingtons counseling. It has
both terrible psychiatric cognitive symptoms and motor dysfunction.
If you have the [mutated] gene, youre going to get the
disease. Do you really want to know? Thats been the controversy
testing and early observation of those with the gene, however,
could help future generations. We really dont know
the first signs of Huntingtons, said Claudia Testa,
assistant professor of neurology. If we help define the
symptoms, it could help in designing future neuroprotective
Professor of Human Genetics Anthony Chan aims to define the
earliest signs of Huntingtons by creating a monkey model
of the disorder. Chan was part of the Oregon Health and Sciences
University group that created the worlds first transgenic
primate in 2000a rhesus macaque with inserted DNA from
a fluorescent jellyfish. Since 2002, Chan has been at Emory,
where he has an appointment at Yerkes National Primate Research
research, says Warren, will allow the creation of rhesus
and rat models of human genetic disease where mouse models are
not sufficient for addressing critical questions of disease
progression, pathology, and potential therapy.
modified monkeys and personalized genetic blueprints sound like
sci-fi thriller material, but Emory geneticists say the reality
is much less alarming.
vast majority of genetics research and testing has been hugely
beneficial to people for decades, says Ledbetter. Sensationalizing
this research or focusing on imagined dangers, Ledbetter says,
could scare patients away from using valuable technologies.
People ask me all the time, How do you deal with
those ethical dilemmas you face every day? But I dont
face any ethical dilemmas. Nothing but positives could come
out of my research. I receive tremendous satisfaction from the
people we help.
babies are born with Down syndrome or other genetic defects,
their parents want to know why this happened. We relieve them
of the incredible guilt they feel that they did something wrong
during the pregnancy. Also, we give them an idea of the likelihood
that they will have another child with the same disorder. This
is good, useful work.
scientists use their high-tech arsenal not only to pinpoint
single-gene disorders, but also to identify genetic mutations
linked to more common diseases, such as cancer.
the genetic causes of disorders such as Down syndrome or Huntingtons
disease are relatively straightforward, other diseases and traits
are caused by a combination of several genes, or an interaction
between genes and the environment. Some adults, for example,
may have a genetic predisposition to alcoholism or Alzheimers
or breast cancer, yet not develop the illness.
Emory has a partnership with deCODE genetics, an Icelandic company
that uses the countrys wealth of genealogy data, homogeneous
population, and willing volunteers to identify the role genes
play in common diseases.
Its interesting and exciting that well be
able to decode genes that definitely will be a new frontier
in cardiology, said Laurence Sperling, director of preventive
cardiology, after deCODE announced it had found a gene that
might double an individuals risk of a heart attack. But
its not that simple. Its not like there are two
genes [for heart disease]; its more like two hundred and
Still, advances in medical genetics are occurring at a prodigious
rate, says Warren, which holds great promise for the development
of new therapies for those already afflicted, as well as for
the maintenance of health in the healthy.