Personalized Medicine: The Role of Genomics in Disease Therapy

In 1990, the United States Department of Energy and the National Institutes of Health began a comprehensive study titled the Human Genome Project (HGP).¹ The 13-year study endeavored to understand the genetic makeup of human beings, and its completion spawned an entirely new field of study called “genomics.” This field of study has had significant influence on the medical community, impacting resources, knowledge and technology surrounding genetic contributions to human health. Because of the HGP, genetics is playing an increasingly important role in the diagnosis, monitoring and treatment of diseases, and the development and prescription of medication.

The History of Genetic Study

Scientists first began an in-depth study of genetics in the early 20th century by applying the plant-based research of Austrian monk Gregor Mendel to the study of human genetics. In 1905, W.C. Farrabee, an anthropologist at Yale University, published a study that described a family with brachydactyly, a dominant genetic disorder in which affected people have very short and stubby fingers. This was the first published scientific report to document the inheritance pattern of genetic disease.²

The discovery of genetic links to disease eventually led scientists to wonder if social and personality traits were genetically influenced as well, which led to a field of study called “eugenics.” Eugenics focused on how to predict and influence traits like intelligence, criminal behavior, poverty and artistic ability through the study of dominant or recessive genes. However, eugenics took a dark turn in the 1930s when Nazis took the concept to the extreme and attempted to rid the world of anyone deemed “genetically impure.” While mainstream eugenics was more or less abandoned afterWorldWarII, many scientists and physicians remained interested in genetic study and the role that heredity plays in diseases and birth defects. As a result, the first medical genetics clinics opened in the United States in the mid-1940s and early 1950s.

Around 1950, a number of discoveries were made regarding the nature of DNA and the structure of the DNA molecule. In 1975, a method to isolate and analyze DNA fragments now known as the Southern blot analysis was discovered and used in genetic testing. By the early 1980s, improved testing techniques helped researchers discover genetic links to disorders like cystic fibrosis, muscular dystrophy and Huntington’s disease.

The past few decades have seen the rapid advancement of genetic testing capabilities, leading to breakthroughs in drug development, disease diagnosis and preventive medical care.

The Emerging Field of Pharmacogenomics

A relatively new area of genetic study focuses on tailoring drugs to an individual’s genetic makeup. Known as pharmacogenomics, this emerging science already is used for several commonly prescribed drugs. Recently, two large prescription drug companies announced plans to offer in-pharmacy genetic testing as part of the prescription-filling process. In effect, certain prescriptions will trigger physician notification about available genetic testing, which will then be offered as an option to the patient. Presumably, the testing will help physicians customize prescriptions to fit individual needs, ward off undesirable side effects and optimize patient outcomes.

“There are still a relatively small number of drugs where pharmacogenomics actually plays a role, but this could drastically expand over the next five years,” says Scott Weiss, a physician at Harvard Medical School and interim director of the Partners HealthCare Center for Personalized Genetic Medicine. “Antidepressants, asthma meds, antiarrhythmia drugs, lipid-lowering drugs — some of the biggest sellers in terms of drug use nationally could potentially have pharmacogenetic implications.”³

Diagnosing and Predicting Disease

The knowledge garnered from the HGP has helped researchers better understand some of the genetic influences that cause or contribute to disease. All diseases have a genetic component, whether inherited or as a result of the body’s response to environmental stresses, such as viruses or toxins. Ultimately, the goal is to learn how a faulty gene might cause disease, and then use this information to treat, cure or even prevent various diseases. Of course, some information gathered from genetic testing is beneficial only from a research perspective; knowing you have a likelihood of developing an incurable disease like Alzheimer’s offers little benefit. On the other hand, some testing in areas like dermatology may provide opportunity for preemptive treatment for common — albeit not life-threatening — inherited conditions, such as male and female pattern baldness.

“Current genetic testing can predict with 80 percent accuracy whether an individual will lose their hair. We can also test patients to see how they will respond to various interventions, saving them the expense and emotional distress associated with ineffective treatments,” says Andy Goren, president and chief executive officer of HairDX, a pharmacogenomics company in Irvine, Calif.

While science is still in the early stages of understanding the genetic link to disorders such as hair loss, certain genes have been identified as a predetermining factor in assessing the likelihood of early-onset baldness. And, since effective medical treatments are available to treat hair loss, identifying this gene in an individual can be beneficial from a clinical perspective. In the future, lessons learned from this type of genetic testing can potentially help patients and physicians better understand the implications of genetic testing for more complex health concerns, especially as such testing becomes more widely available.¹

Gene Therapy and Drug Design

Thanks in large part to breakthroughs in genetic studies, research and development of future pharmaceuticals are shifting away from diagnostics and toward developing new-generation therapeutics based on genes. This opens the door for entire new classes of medicines based on gene sequence and protein structure, as opposed to traditional trial-and-error methods.

The potential for using genes themselves to treat disease is another exciting application of DNA science. This rapidly developing field holds great potential for treating or even curing genetic and acquired diseases by using normal genes to replace or supplement a defective gene or to bolster immunity to disease. In recent studies, gene therapy has been used successfully to cure deafness in guinea pigs, to restore vision in dogs and to reduce the size of human lung cancer tumors in mice.⁴

Ethical Issues Remain

The amount of gene-related research and development occurring in the United States continues to grow at a fast rate, as do certain ethical, medical and social concerns. Proponents of genetic testing to predict disease argue that genetic-risk information should be viewed just like any other risk information, such as high cholesterol levels, and that consumers have a right to that information. Opponents argue that the testing is not clinically proven and can be difficult to interpret; an individual with a 75 percent chance of developing a particular genetic disease may remain healthy throughout his or her life, while an individual with only 25 percent probability of disease development may end up succumbing to it. Privacy issues related to employment and qualification for health insurance also come into play.

Still Moving Forward

The U.S. Food and Drug Administration is currently fielding numerous requests from medical researchers and manufacturers to study gene therapy and to develop gene therapy products. Such research could lead to gene-based treatments for cancer, cystic fibrosis, heart disease, hemophilia, wounds, infectious diseases such as AIDS, and graftversus-host disease.