Whole genomes and personalised medicine: where are we heading?

Last week I gave a number of invited lectures in Queensland and Tasmania about genetic heart diseases, sudden death in the young, and the key role of genetic testing in diagnosis and targeting disease prevention. In one of the lectures, I was asked to give a specific prediction related to my lecture topic. Considering my thoughts about human disease, the role of genetics, and the prolific advances in genetic technologies, my specific prediction was as follows:

“By 2016, 50% of the adult population in developed countries will have their own entire genome completely sequenced”.

What do you think? Well here is my simple thinking behind this prediction, with two main points.

The first point is the increasing availability and decreasing cost of whole genome sequencing. When the first whole genome (i.e. sequencing all ~23,000 genes that we each have) was sequenced and completed in 2000, the cost for this one whole genome was $US3 billion! As one can see from the graph attached (adapted from The Economist), later in 2012, the cost of sequencing a whole genome (red line) will be under $US1000. As a result, the genome is now within reach of many in our populations, both in terms of cost and availability. This is dramatically reflected in the exponential increase in the number of people who are already having their genomes sequenced! The black line in the graph shows the dramatic increase in the number of genomes sequenced over recent years (note the log scale of the y-axis!).

The second point is the potential value of knowing your whole genome. The genetic information for an individual person is mind blowing. Broadly speaking, there are two types of relevant genetic information involving DNA variations (changes in our genetic sequences). The first group of genetic variations may directly cause disease, such as we see in cardiomyopathies, long QT syndrome, cystic fibrosis, multiple sclerosis, and various genetic syndromes. The second group of genetic variations may not directly cause disease, but are associated with risk of disease, such as the risk of developing diabetes, cancer, or Alzheimer’s disease, as well as predicting how people will respond to different drug therapies (so called “pharmacogenomics”).

Collectively, understanding our genetic risks provides an important platform for early diagnosis, initiation of pre-clinical treatment and monitoring strategies, and in some cases, provision of early opportunities for prevention therapies. As a clinician, the greatest promise of whole genome information is to optimise care of patients, and to reduce the risks of developing disease and its related complications.  The understanding that each person in the world is genetically unique provides the basis for individualised care, or personalised medicine, whereby each person may be treated slightly different depending on their genetic make-up. The benefit of such strategies holds great promise.

Of course, there are many issues that arise in the setting of whole genome sequencing that must be considered, debated, and discussed. While we can sequence every gene in our bodies, medical research is nowhere near understanding what each gene in the body does, and how changes in the sequence of the specific genes lead to disease. There are also many ethical, moral and legal issues that need to be worked through as we learn more about whole genome sequencing. Do we really want to know what diseases we will get in 5, 10 or 20 years? Will our life insurance companies want to know our genetic risks? What are the implications for genetic screening at birth, or prenatally, or even pre-implantation? The number of questions posed is substantial. However the reality is, whole genome sequencing is now more readily available, the cost is now affordable, and there are already clear trends that people around the world want to have the testing performed.

The next few years will be a fascinating and exciting journey. Whether its 50% or 5% of the population by 2016, and irrespective of the potential issues, whole genome sequencing for humans is here. It represents the most exciting phase in human genetics that we will see in our lifetimes. The potential impact of genetic knowledge on how we can identify disease risk is the most exciting aspect, as it will then provide opportunities for early diagnosis, treatment, and prevention, and facilitate our ultimate goal to prevent disease and improve human health.

Prof Chris