July 14, 2011
As the physician Hippocrates taught us, “It is more important to know what person the disease has than what disease the person has.” Today, 2,400 years later, science is revisiting this tenet: our understanding of the genetic differences between individuals will soon provide a basis for personalized medicine. After all, around 30 to 80 percent of patients today derive no benefit from the medications they are receiving for a range of common conditions – some drugs and certain doses are actually hazardous for individual patients. There is no question that a paradigm shift toward specific, evidence-based and personalized medicine would be a great step forward.
Doctors are already able to choose specific drugs based on the patient’s gene variants. The discovery that certain gene variants affect the way in which an individual responds to the components of a drug is itself an important addition to our knowledge. This has given rise to a new area of research: pharmacogenetics or pharmacogenomics, which aims to harmonize drugs and dosages with the patient’s genetic profile. There are known genetic variants that affect the way patients respond to cholesterol-reducing drugs, anticoagulants, AIDS treatments, antidepressants and other common prescription drugs.
New diagnostic procedures also allow us to step up the fight against cancer. The basis lies in molecular genetic studies of the tumors themselves. A prime example of this form of personalized medicine is Herceptin – a therapeutic antibody used by doctors to treat a certain form of breast cancer. One of the defining features of these tumors is that large quantities of the protein HER2 are produced on the surface of the tumor cells, stimulating cell growth. Herceptin can interrupt the protein function and thus also the growth of the tumor. At the same time, it also activates the body’s own immune cells in order to kill off the cancer cells.
The active ingredient is the product of research by Axel Ullrich, Director at the Max Planck Institute of Biochemistry in Martinsried. In the meantime, other approaches to the treatment of cancer are adopting his model, which combines molecular diagnostics and therapy.
The hope that decoding the human genome would lead directly to rapid progress in the field of medicine has, as yet, barely been fulfilled. The number of monogenetic diseases – those that derive from a defect in a single gene – is comparatively small, and the diseases themselves quite rare. Most widespread diseases are associated with multiple genetic mutations.
In addition, genetic regulation and a number of environmental factors play an important role in the way diseases manifest themselves. However, it is known that specific genetic variants increase the risk of contracting some chronic illnesses, such as coronary heart disease, diabetes and Alzheimer’s. Corresponding studies may provide a basis on which to develop preventive treatments for patients with a disposition toward certain diseases.
Still, if we are to derive a sustainable prognosis from an individual genome, there are other factors that science must be aware of. It is a matter of aligning the genomic data with the phenotype, that is, the various features of the organism concerned. Genomic and genetic testing procedures must be supplemented by technologies with the ability to create molecular fingerprints, such as transcriptome, proteome and metabolome analyses.