Personalized medicine: the panacea is late

A few years ago, the current head of the American National Institutes of Health (NIH), Francis Collins, quite convincingly represented the coming era of personalized medicine as the final victory of mankind over diseases, promising a universal remedy for universal health and the eradication of the most serious diseases. It is not difficult to guess that, as in the case of other "panaceas of the century", the promised miracles of healing, to put it mildly, are late with their appearance, and perhaps they are nothing more than a figment of the imagination of science fiction writers. What is the true state of things today and what to expect from personalized medicine?

First of all, let's remember the "three whales" on which the expectations of personalized medicine are based.

• Firstly, the genome of each person can be easily and inexpensively decoded and the information obtained can be used to predict probable diseases, prevent them and develop an individual treatment method.
• Secondly, most of the diseases predicted as a result of genome decoding can be prevented through genetic or therapeutic methods, as well as lifestyle correction.
• And, finally, thirdly, the diseases that arise in the patient will be treated with the help of individually developed drugs that take into account the characteristics of the body and the nature of the disease. Minimum risk, minimum complications, minimum problems.

But both consumers of medical services and the scientific community today face a completely different reality.

The $1,000 genome sequencing method promises to become available in the near future and represents an incredible achievement of biotechnology. But this does not promise a breakthrough in medicine. The method will not be of any use if the interpretation of the gene sequence costs $10,000 and does not provide comprehensive information. Most diseases are caused by a large number of different genes, each of which individually exhibits an inconspicuous effect, which makes it difficult to objectively assess the degree of risk of a particular combination of genes. In addition, gene expression products interact with each other and with external factors. But the most important thing, perhaps, is that our idea of a particular disease as a single process may be erroneous, and the disease may represent a combination of heterogeneous, rare disorders.

The human genome is like a moving target. For example, variation in the number of copies of genes (copy number variations, CNV), DNA segments occurring in different numbers in different genomes is a fairly common phenomenon. More recently, scientists have identified a link between microdeletions and microduplications, as a result of which the number of copies at a certain locus changes, with autism (J Med Genetics, Sept 24, 2009, electronic version). Changes of this nature are not found in the genomes of both parents. In fact, if the sequence of the genome may differ even in individual cells, our body is a mosaic of very similar, but still different genomes. To overcome this difficulty, it is necessary to combine several technologies. Researchers have already done something in this direction. Large-scale scanning of the genome along a shorter path leads to an understanding of the mechanisms of the disease, eliminating the need for complex biochemical and physiological studies.

Pharmacogenomics, a new branch of pharmacology, is also keeping up with progress and making significant progress. Pharmacogenomics correlates the genetic characteristics of the patient with the effectiveness of the drug, and also evaluates its individual tolerability, which is really very important, since adverse reactions to drugs account for a significant percentage of hospitalizations of patients. Currently, only about 10 tests are known on the medical market that allow determining the individual susceptibility of a patient to a number of drugs. All of them represent simple DNA tests for SNIP markers (SNP – single nucleotide polymorphism - single nucleotide polymorphism), but even this technology marks an important milestone in the development of personalized medicine, leaving the appearance of multigenic tests only a matter of time.

Representatives of the pharmaceutical industry, for their part, give a positive assessment of the development of pharmacogenomics in the hope of saving the reputation of some drugs that have failed clinical trials due to high toxicity or insufficient effectiveness for the group of subjects as a whole. The essence of the idea is extremely simple: relying on genetics, to identify patients susceptible to the drug, thereby increasing the effectiveness and eliminating side effects of the drug, which will give doctors truly effective, viable means.

Other commercial projects on "customer genotyping" have not been successful. A handful of companies continue to engage in ridiculous pedigree compilation, banal character description and useless compilation of lifestyle recommendations. It will take a long time before they become really useful, and the well-known phrase "it is more natural for a person to buy than to think" is ideal for ordering such pseudoscientific tests.

To put it in a high style, knowledge is the opposite of ignorance. Scientific progress continues to dispel our misconceptions about diseases. While scientists are clearing up the obstacles of unresolved problems on the way to personalized medicine, do not forget about other approaches to disease prevention – healthy eating, sports, fighting bad habits.

Ruslan Kushnir
Eternal Youth Portal www.vechnayamolodost.ru based on the materials of The Scientist: Stumbling Towards Nirvana

21.12.2009