by Yusuke Nakamura Human Genome Center Tokyo I believe the human genome project is leading us towards an ideal custom-made kind of medicine, free of side-effects, prescribed from an understanding of the idiosyncrasies of our genes.

The numbers are huge, but we are learning how to characterise genes – genotyping – so that their patterns will tell doctors when and how to treat a specific person.

Just as each person has his own face, so from person to person DNA sequences that are owned by the genome differ. This genetic variation is known as genetic polymorphism.

Among several types of DNA polymorphism, single nucleotide polymorphisms (SNPs) are considered to be the most important polymorphic markers today. Among the three billion nucleotides of the genome, SNPs are located at up to ten million places. Novel techniques and rapid analysis systems for SNP genotyping on a large scale are beginning to come to fruition. They should contribute significantly to medical science. In the near future we will be seeing its application for the rapid diagnosis and treatment of patients.

Our bodies are composed of 60 trillion cells and, with some exceptions, each cell contains the same DNA sequences in their nuclei. However, it is clear that each cell has its own specific characteristics, and even plays a crucial role in maintaining homeostasis, the stability of our body.

In order that each cell can carry out its designated function, essential proteins must be synthesised in accordance with the genetic information at the appropriate time, and in exactly the right quantities. To put it another way, our health in everyday life is maintained under changing conditions by making appropriate use of the program encoded in the genome, and controlling the expression of its 30,000 or so genes. However, genetic variations and environmental factors can conspire to upset this control mechanism. This can lead to over or under production of essential proteins, or to the loss of their original function or activity.

As a result, an imbalance arises among the various substances necessary for the support of life and activity. We become ill. Hence, it is obvious that differences in the genetic variations, such as SNPs, exert an influence on susceptibility to disease. This is because some genetic polymorphisms, depending on their position, can influence the expression levels, or affect the function or activity of the protein by altering its amino acids. Furthermore, these genetic polymorphisms can become useful tools in identifying the genes associated with a given disease.

As genomics research is further advanced, our understanding of the biological function of each gene product, and of the mechanism governing when, where and how much of each gene product is produced, is growing rapidly.

It will become possible to understand what sort of imbalance is occurring in cells and tissues in the pathological condition, and the detailed mechanisms underlying diseases. Consequently, through the genome-based approach, we can anticipate the following advances in the medical field:

Targeted medicine
Development of novel diagnostic and therapeutic methods that target the molecules (genes and proteins) causing symptoms and diseases on the basis of a precise understanding of molecular pathology. This is called evidence-based drug development.

Personalised medicine
Patients with similar symptoms, or who are diagnosed to have the same disease, will be differentiated by differences in mechanisms underlying their illness. They will be prescribed ‘personalised’ medication based on these differences.

Prophylactic medicine
By assessing a person's risk to particular diseases through genetic testing it will be possible to avoid disease, to delay the onset of disease, or to treat at an early stage by taking care of lifestyle and/or frequent clinical examination.

In contrast to medical treatment in the last century, the 21st century style medical treatment, brought to us through the genome project, will be symbolised by the term ‘personalised’ medicine. We made unprecedented progress in medical treatment in the last century. But we are still unable to predict the efficacy and side-effects of medicines for a given patient. Medicine is a double-edged sword. An abnormality in the metabolising pathway of a medicine can produce toxic concentrations in tissues or serum. Sometimes it is enough to kill the patient.

Medical treatment today is designed like ready-made clothes, to fit most but not all. I believe the human genome project is leading us towards an ideal custom-made kind of medicine, free of side-effects, prescribed from an understanding of the idiosyncrasies of our genes.