Personalized Medicine — How Genetics and Genomics are Transforming Healthcare

Kucherlapati, Raju, PhD
Paul C. Cabot Professor of Genetics
Professor of Medicine
Harvard Medical School
Boston, MA
Also by this Author 

Personalized medicine has gained much attention following the announcement of a national initiative to fund “a new model of patient-powered research…to accelerate biomedical discoveries and provide clinicians with new tools, knowledge, and therapies to select which treatments will work best for which patients.”1

Dr. Raju Kucherlapati, Paul C. Cabot Professor of Genetics, Harvard Medical School, discusses the genetic basis for personalized medicine, reviews the ways in which it is identifying susceptibility to disease, and discusses how it is transforming the way diseases are diagnosed and treated.

Identifying the Genetic Basis for Disease

“Personalized medicine is the use of genetic and genomic information for accurate diagnosis, prognosis, and treatment decisions,” says Dr. Kucherlapati. “It is also referred to as precision medicine but the two terms essentially refer to the same approach.” It is an approach resulting from our understanding of the genetic basis of disease, which has evolved over a long period of time but has been transformed as a result of the human genome project.

“It’s been known for more than 100 years that there are certain types of human diseases, which have a genetic basis,” continues Dr. Kucherlapati. “But for a long time people really thought about them as rare genetic disorders and did not appreciate that genetics actually plays a very important role in virtually all aspects of human health.”

“Today, for example, it’s generally recognized that the most important set of diseases that affects the U.S. population is obesity and diabetes. These affect more than 5% of the population and the number is increasing very, very rapidly. So the question that could be asked of these complex diseases is: do they have a genetic basis? This has been established by studies conducted on sets of identical and fraternal twins. When you look at identical twins, it turns out the so-called concordance rate (both members of the twin pair developing the disease) is 95% in identical twins; and in fraternal twins, it's less than 50%.  So that's a dramatic illustration that obesity and diabetes have a genetic component to them. These types of studies have also been done for autoimmune diseases, such as rheumatoid arthritis, psychiatric illness like schizophrenia or bipolar disorder, movement disorders such as Parkinson's Disease and for Alzheimer's Disease. We now understand that all of them have a genetic basis.”

Sequencing the Human Genome – the Diagnostic Key

Having identified that diseases have a genetic basis, the next step to enable diagnosis was to identify the genes in question and their defects, which was significantly enhanced after completion of the human genome project. “Mapping and sequencing the human genome allowed us to compare DNA sequences from any two groups of individuals, one with a disease and one without, look at what’s missing or changed in the person with the disease, and thereby identify the disease gene,” says Dr. Kucherlapati. “However, to achieve this you needed to sequence the genomes of many, many people. Initially this was impossible because of the huge cost involved but it is now becoming a reality due to the remarkable decline in cost of sequencing the human genome using next generation sequencing technology. As costs have come down, sequencing is starting to increase, helping to establish DNA databases, both in the U.S. and overseas. “With these initiatives underway the amount of genetic information available is already very, very significant”, notes Dr. Kucherlapati.

Disease Prevention

In considering the various ways in which the understanding of genetic disease can impact an individual’s well-being, Dr. Kucherlapati, starts with disease prevention. “Clearly, if we were able to prevent disease in the first place it would have a dramatic impact on human health and on healthcare cost,” he notes. “There are some dramatic examples of situations where it is possible either to eliminate or reduce the incidence of certain types or devastating diseases. With Tay-Sachs disease, for example, it is possible to test individuals, to determine whether they carry the susceptibility gene in their DNA. In the case of the Ashkenazi Jewish population, a screening program was implemented to identify whether someone was a carrier. Informed decisions could then be made regarding the choice of future spouse or undergoing pre-natal testing and, as a result, Tay-Sachs has completely been eliminated in that population over the last 20 years or so.”

Risk-assessment using genetic tests is also providing the basis for identifying cancer susceptibility, such as for breast and ovarian cancers. If patients have a mutation, which increases their disease susceptibility, they will be presented with options to decrease their risk, such as surgical or chemotherapeutic intervention, or hormonal manipulation.

Clinical Application - Pre-Natal Testing       

One area benefiting from genetic testing is pre-natal testing. In the United States, it’s recommended that a woman who becomes pregnant when she's 35 years or older undergoes fetal testing. Until very recently a popular method available for this was amniocentesis. “In 2011, it was discovered that there is a little bit of fetal DNA circulating in maternal blood, and that obtaining a small amount of blood from the mother is sufficient to test the status of the fetus,” says Dr. Kucherlapati. “Because of next generation sequencing, we don't need very much DNA to perform this kind of test. So you can imagine what the decision is going to be, if a woman is given the choice between a trans-abdominal needle or venipuncture. This is completely transforming the way that prenatal diagnosis is performed.”

Neonatal Screening

In the United States, a drop of blood is drawn from every newborn child and is used by state laboratories to test for so-called biochemical disorders. “Many of those labs do testing for about 20 different genetic defects,” says Dr. Kucherlapati, “but now, with these new technologies, it's possible to take the DNA that comes from a drop of blood and test for hundreds of genes. This allows you to find out whether the children are born with abnormalities in which early intervention is possible.”

There are many examples in pediatrics of how next generation sequencing and the approach to personalized medicine provide a basis for risk assessment and diagnosis. “It turns out that there are some children born with disorders whose etiology is not known but can be identified as a result of genetic testing,” says Dr. Kucherlapati. “This, in turn, is enabling physicians to find appropriate therapies for them.” 

Refining Cancer Diagnosis and Therapy

Cancer traditionally has been categorized based upon its organ of origin. “It actually turns out”, notes Dr. Kucherlapati. “that cancers, such as breast and lung cancer, are not homogeneous but different. Lung cancer can be classified into 15 different categories based upon the genetic changes that are present, and breast cancer can be classified into 10 different categories based on genetic changes. There is either a drug that's already approved by the Food and Drug Administration, or a drug in development, that targets the particular genetic change that is present in each of these tumors. This has already changed the course of the disease in some cancers and it's promising to change the course of disease in all cancers.”

Changing the Course of Disease

“I think that for many different conditions, as our knowledge increases, both about the genetics and the disease as a whole, our ability to make predictions or determine the prognosis for patients and our ability to develop therapeutic approaches is going to increase rapidly. It is now plausible to say, for example, that cancer will become a chronic disease due to our greater knowledge and capabilities. Personalized medicine is going to become fundamental in terms of biological discovery and the practice of medicine, using genetic-based testing and therapies.”



  1. Fact Sheet: President Obama’s Precision Medicine Initiative. The White House.  Accessed April 27, 2015