How it came to be here, in Emory’s 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.”

The 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 straight–perhaps even if we will be shy or outgoing, or prone to Alzheimer’s or obesity.

Over 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.

Critics occasionally decry this burgeoning genetic experimentation, claiming that scientists and biotech companies are opening a Pandora’s box with unpredictable consequences. But, in truth, the box already has been opened.

In 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 chemicals–adenine, cytosine, guanine, and thymine, abbreviated A, C, G, and T. The project would determine the sequences of the genome’s 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 medications.

By June 2000–years ahead of schedule and under budget–scientists released the first rough draft of the genome. President Bill Clinton called it the “most important, most wondrous map ever produced by mankind.”

Around 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.

“This 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.”

In 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.

The 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 Center–one of three in the country.

In 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.

Robert 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.

“Everyone talks a great deal about translational research–‘from the bench to the bedside’–but 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, we’ve got it all–the 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.”

Emory’s 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.

PKU 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 physical disabilities.

Treatment consists of a carefully controlled diet begun during the infant’s first days or weeks, which often must be followed for life. Frequent blood monitoring is necessary.

“Our relationship with these families can begin as soon as their infants are screened,” says Rani H. Singh, assistant professor and director of the department’s nutrition section. “We want to demonstrate how good nutritional management can improve outcomes and the quality of life for our patients.”

About 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 mother’s womb during in vitro fertilization.

Scientists say that in the not-too-distant future it might be possible to sequence an individual’s genome for as little as $1,000, providing a personal guide for predicting susceptibility to diseases and choosing the most appropriate treatments.

To gain knowledge of one’s genetic fate, however, delivers its own complications. A case in point is Huntington’s disease, a degenerative neurological disorder that strikes one in ten thousand and doesn’t 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 Huntington’s has a fifty-fifty chance of inheriting the gene.

“It’s a horrible disease,” said Randi Jones, an Emory neuropsychologist who specializes in Huntington’s counseling. “It has both terrible psychiatric cognitive symptoms and motor dysfunction. If you have the [mutated] gene, you’re going to get the disease. Do you really want to know? That’s been the controversy all along.”

Genetic testing and early observation of those with the gene, however, could help future generations. “We really don’t know the first signs of Huntington’s,” said Claudia Testa, assistant professor of neurology. “If we help define the symptoms, it could help in designing future neuroprotective drugs.”

Assistant Professor of Human Genetics Anthony Chan aims to define the earliest signs of Huntington’s by creating a monkey model of the disorder. Chan was part of the Oregon Health and Sciences University group that created the world’s first transgenic primate in 2000–a 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 Center.

Chan’s 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.”

Genetically modified monkeys and personalized genetic blueprints sound like sci-fi thriller material, but Emory geneticists say the reality is much less alarming.

The 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 don’t face any ethical dilemmas. Nothing but positives could come out of my research. I receive tremendous satisfaction from the people we help.

“When 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.”

Emory 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.

While the genetic causes of disorders such as Down syndrome or Huntington’s 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 Alzheimer’s or breast cancer, yet not develop the illness.

Emory has a partnership with deCODE genetics, an Icelandic company that uses the country’s wealth of genealogy data, homogeneous population, and willing volunteers to identify the role genes play in common diseases.

“It’s interesting and exciting that we’ll 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 individual’s risk of a heart attack. “But it’s not that simple. It’s not like there are two genes [for heart disease]; it’s more like two hundred and fifty.”

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.”



© 2004 Emory University