A brief history of medical genetics and Emory’s team
By Michael J. Gambello, MD, PhD
Medical genetics is a relatively new subspecialty that is a mystery to many healthcare providers as well as the general public. We hope to unravel some of this mystery in this issue of Atlanta Medicine and enlighten you on some aspects of our practice at Emory.
At Emory, we do diagnose and manage rare diseases, which collectively are not that rare – but this is not exclusively so. Medical genetics involves the diagnosis and management of hereditary diseases, or the “science of human biologic variation as it relates to health and disease,” to quote Victor McKusick1, one of the fathers of medical genetics.
In spite of these definitions, our daily role is still not clear. However, by looking at the history of medical genetics and Emory’s role in this fascinating and technology-laden world, perhaps these definitions can be put in a better perspective.
A Brief History of Medical Genetics
Many clinicians noted familial segregation of disease before medical genetics surfaced as a young specialty in the 1950s. Over the next several decades, major discoveries in the basic science of human genetics led to the development of medical genetics. Noteworthy areas of discovery occurred in cytogenetics (the study of chromosomes), inheritance of discrete traits (sometimes called Mendelism, after Gregor Mendel’s studies on wrinkled and round peas), biochemical, population and molecular genetics.
The 1950s were transformative years. In 1953, Watson and Crick, using important data from Franklin and Wilkins, discovered the double helical structure of DNA, noting “it has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.”2
In 1956 Tjio and Levan developed a novel method to analyze chromosomes under the microscope and determined that humans have 46 chromsomes 3. In 1959 Lejeune showed that an extra chromosome 21 was the cause of Down syndrome, soon to be followed by the chromosomal nature of Turner syndrome and Klinefelter syndrome1. During this time, the central dogma of molecular biology was also established: DNA is transcribed into RNA that is translated into protein.
The genetic code was “broken” in 1966 by the combined work of Holley, Khorana and Nirenberg and others. A three nucleotide codon specifies which amino acid will be incorporated into a protein. The first World Congress of Human Genetics was held in Copenhagen in 1956. The first chair of Medical Genetics, Maurice Lamy, was appointed in Paris. In 1957, specific medical genetics departments open in Baltimore (Victor McKusick at Johns Hopkins) and Seattle (Arno Motulsky at the University of Washington).
Victor McKusick, considered the father of medical genetics by many, published Mendelian Inheritance in Man (MIM), a catalogue of autosomal dominant, autosomal recessive and X-linked phenotypes. The exponential increase in genetic knowledge has transformed MIM to OMIM – Online Mendelian Inheritance in Man – A catalogue of Human Genes and Disorders.
In 1977, Sanger developed a novel method of sequencing DNA, and the molecular era was full speed ahead. Using families and linkage analysis, gene identification and mapping for many Mendelian disorders were accomplished. In 1991, the American Board of Medical Genetics (ABMG), became the 24th organization to join the American Board of Medical Specialties. This board gives oversight to the training and practice of medical genetics.
By 1984, plans were underway to determine all the A’s, T’s, G’s and C’s that comprise the human genome, called The Human Genome Project. The project began in 1990 and was finished in 2003. It is amazing that only about 1 percent of the genome actually codes for genes (termed the exome) and that we only have about 20,000 genes. (Given the size of our genome, it was thought that we had at least 100,000.) The remaining 99 percent of our genome appears to regulate gene expression, but there is still much research to be done.
Over the past 10 years, DNA sequencing technologies (called massively parallel sequencing) have improved tremendously, permitting whole exome sequencing (only 1 percent of the genome, i.e. coding genes only) for diagnostic testing in medical genetics. The next technology challenging medical genetics is whole genome sequencing. While The Human Genome Project cost $2.7 billion and took 13 years, a whole human genome now costs about $2,000 and can be done within a week.
Indeed we are in the genomics age, where we are now sequencing, assembling and analyzing the function and structure of genomes. Recently the ABMG changed its name to the American Board of Medical Genetics and Genomics to reflect the importance of genomics in our practice.
Medical genetics has indeed evolved quickly in just over 60 years. Today, there are many Medical Genetics Departments and Divisions throughout the U.S. that assist healthcare givers and patients navigate the rapidly advancing field of medical genetics.
The Division of Medical Genetics at Emory
The Division of Medical Genetics at Emory University School of Medicine (genetics.emory.edu) was founded in 1970 by Louis “Skip” Elsas II, M.D. Medical genetics was then part of the Department of Pediatrics to reflect a heavy emphasis on pediatric medicine. In 2001, Stephen Warren, Ph.D., founded the Department of Human Genetics at Emory. By 2002, the Division became formally affiliated with the Department of Human Genetics.
This structure reflects an important historical and synergistic relationship between the clinical and basic sciences. While we certainly still care for many children, our practice has a much larger scope. The Division is composed of a variety of genetic providers, including physicians (the medical geneticists), genetic counselors, metabolic nutritionists, nurses, psychologists, a developmental pediatrician and other support staff.
Medical geneticists are physicians who have completed a two-year ACGME (Accreditation Council for Graduate Medical Education) accredited program in medical genetics. Typically, physicians who train in medical genetics have already completed a residency in a primary care specialty such as pediatrics, internal medicine, family medicine or obstetrics-gynecology.
Medical geneticists are encouraged to become Board Certified by the American Board of Medical Genetics and Genomics. The Board exists to protect the public by maintaining high standards for the practice of medical genetics. Emory has an ACGME-accredited training program in medical genetics (genetics.emory.edu/education). We provide inpatient consultation for Children’s Healthcare of Atlanta at Egleston/Scottish Rite and Emory University Hospital.
We have about 4,000 outpatient visits a year, and we anticipate 5,000 next year. Our patient population is diverse, and the subsequent sections of this issue will help you understand the scope of our practice and when your patient might need a consultation with the medical genetics team. Keep in mind that our mission is not only excellent patient care, but also research and teaching. Many of us are involved in discovering the genetic causes of new disease, conducting clinic trials, and teaching in the classroom and clinic.
Genetic counselors are health professionals who form an integral part of the medical genetics team. They complete a two-year ACGC (Accreditation Council for Genetic Counseling) accredited graduate program to gain experience in medical genetics, research and counseling. Students come from a variety of disciplines such as biology, nursing, social work, psychology and public health. The National Society of Genetic Counselors states that “genetic counseling is the process of helping people understand and adapt to the medical, psychological and familial implications of genetic contributions to disease.”
In practice, their role varies widely. Some functions include taking medical and family histories, coordinating and interpreting genetic testing to patients and healthcare providers, coordinating clinical trials and teaching. Emory has an ACGC-accredited training program (genetics.emory.edu/gc_training) and is always looking for enthusiastic students.
Metabolic dietitian is another highly specialized profession. These healthcare providers help care for patients with inborn errors of metabolism, or biochemical genetic disorders. Some of these disorders result from a genetic defect in an enzyme that is important for detoxifying too much of a metabolite, or making energy. Most readers are familiar with phenylketonuria (PKU) – the inability to breakdown excess phenylalanine. Adherence to a strict diet from infancy prevents severe intellectual disability. In fact, the success of dietary treatment for PKU was a major impetus for the introduction of newborn screening programs that will be discussed in a subsequent section. We now screen for more than 30 disorders and identify many children and families who benefit from the expertise of a metabolic dietitian.
In this issue of Atlanta Medicine, you’ll find articles by many of my colleagues about various aspects of medical genetics, from infancy to adulthood. We have omitted prenatal genetics, which is managed almost exclusively by Maternal Fetal Medicine experts at Emory and other programs, though we often communicate with them when addressing reproductive options for families.
We hope that these brief articles will better define what we do and how we might be able to help you and your patients. Rossana Sanchez, M.D., is a trainee in our medical genetics residency. She gives you a concise description of when your patients might benefit from a medical genetics consultation. Suma Shankar, M.D., Ph.D., reviews aspects of medical genetics and pediatrics. Hong Li, M.D., Ph.D., gives an excellent description of newborn screening programs and biochemical genetics. Jaime Vengoechea discusses some genetic disorders of adult medicine. Bill Wilcox, M.D., Ph.D., demonstrates that we are not merely diagnosticians, but do indeed treat many genetic diseases.
- McKusick VA and Harper PS. 2013. History of Medical Genetics. In:Rimoin DL, Pyeritz RE, Korf BR ed. Emery and Rimoin’s Principles and Practice of Medical Genetics. Elsevier pp.1-39.
- Watson JD, FHC Crick. Molecular structure of nucleic acids.1953 Nature 171:737-738.
- Tjio JH, Levan LA. 1956. The chromosome number of man. Hereditas 42:1-6.
- UK Genetics Archive Project (<www.genmedhist.org/Records>).
- Human Genetics Historical Library (see <http://www.genmedhist.org/HumanHistLib/>). A collection of over 3000 books.
- Harper, P. S. A Short History of Medical Genetics; Oxford Univer- sity Press, 2008.