04 March 2010

Personalized medicine today and tomorrow

Researchers spent 13 years and 3 billion US dollars sequencing the first human genome. It should be noted that this genome did not belong to a single individual, but was a collection of genetic material from several volunteers. Thanks to the advent of new technologies in recent years, the cost of reading an individual genome has decreased thousands of times, and the time spent on its implementation has been reduced to several tens of days, which has significantly increased its accessibility to the population. Some experts believe that within the next two years, the cost of sequencing an individual genome will overcome the threshold of $ 1,000.

The human genome consists of approximately three billion pairs of nucleotide bases,
and the size of the genome in binary calculus is 778 megabytes.

One of the key aspects of reducing the cost of DNA sequencing technology is the miniaturization of equipment, which reduces the amount of expensive chemicals spent on analysis. Companies working in this direction create various variants of microfluidic chips. For example, BioNanomatrix claims that the diameter of the channels in the devices developed by its specialists is only 50 nanometers, which will someday reduce the cost of sequencing one genome to an incredibly small amount – $ 100.

To date, the leader in the development of DNA sequencing equipment is the company Complete Genomics, established four years ago in Mountain View (California). The technology developed by the company allowed its specialists to sequence 50 human genomes in 2009. In 2010, the company plans to increase the volume of work to 5,000 individual genomes and subsequently keep the bar at 10,000 genomes per year. Moreover, according to the company's statement, the cost of sequencing one genome will be from $ 1,500 to $ 5,000.

The company uses automated systems for DNA sequencing. The high speed and relatively low cost of research carried out with their help is due to the possibility of applying more than a billion amplified DNA fragments to one slide. Placing such a huge amount of information on one slide not only significantly reduces the analysis time, but also reduces the amount of materials used and expensive reagents. The company does not sell its technology in the form of equipment, reagents and software, but provides sequencing services to researchers. Scientists interested in receiving such services send their samples (one order must consist of at least 8 genomes, the maximum number of genomes is not limited) using the FedEx express postal service.

To date, the company is exclusively engaged in meeting the needs of researchers who have already placed a huge number of orders, the volume of which varies from tens to hundreds of genomes. After the excitement in the scientific community subsides, Complete Genomics plans to enter the consumer and medical markets. According to experts, due to the rapid fall in sequencing prices, these markets will actively develop in the near future. In addition to sequencing the genomes of newborns (which in the USA alone means more than four million genomes annually), a promising area of work is the sequencing of tumor DNA, which will maximize the effectiveness of antitumor therapy.

According to the company's executive director Clifford Reid, the company has Napoleonic plans. It plans to open 10 branches around the world, which will allow it to sequence one million genomes over the next five years.

Currently, the following companies offer services for sequencing individual genomes and identifying genetic variants in the consumer market:

Company Technology and cost

You get information about:


Mountain View, California

micro-sets to identify genetic variants

their origin, the risks of developing diseases, the status of a carrier of hereditary diseases and sensitivity to certain drugs

deCode Genetics
Reykjavik, Iceland

micro-sets to identify genetic variants

their origin and genetic predisposition to various diseases, including various types of cancer

DNA Direct
San Francisco, California

depends on the subcontractor
$175-3 456

the risks of developing more than ten diseases, including cystic fibrosis and breast cancer

Cambridge, Massachusetts

genome-wide sequencing
$68 500

the sequence of the entire genome (attached is an analysis done by a group of researchers)

Redwood Shores, California

micro-sets to identify genetic variants

genetic predisposition to dozens of diseases, including Alzheimer's disease, type 2 diabetes and various types of cancer

Pathway Genomics
San Diego, California

various systems for the analysis of genetic variations

the risks of developing up to 90 diseases, their origin, the status of a carrier of hereditary diseases and sensitivity to certain drugs

Unfortunately, an individual will be able to derive real benefits from the knowledge of his genome only when personalized medicine is finally fully integrated into the existing healthcare system. To date, its principles contradict the officially accepted procedures for the approval of medicines. The standard scheme of clinical trials involves testing the drug on a large heterogeneous group of patients, whereas the whole point of personalization of the drug is its use for the treatment of a genetically specific part of the population that will benefit the most from treatment. The US Food and Drug Administration (FDA) is already attempting to compile protocols for assessing the suitability of drugs developed for the treatment of representatives of certain genetic populations, while simultaneously determining their safety for other individuals who may receive them for undocumented use (for the treatment of diseases not specified in the instructions approved by the FDA).

Last fall, the FDA approved the position of a genomics expert, whose task is to coordinate the efforts of the Department aimed at solving issues related to genetic information and prescribing drugs.

One of the first difficult tasks to be solved by the Department is to evaluate the effectiveness of tests to identify genetic variants and biomarkers designed to identify patients who can benefit the most from taking a particular drug. The Department has already begun to make recommendations for conducting preliminary diagnostic testing in the instructions for certain drugs, and in some cases even the requirement of mandatory genetic testing. However, to date, the process of official approval of the drug-test complex has not yet been put on stream and it is unclear how the FDA will cope with the difficulties associated with the approval of two fundamentally different products within the same protocol.

The drugs that the U.S. Food and Drug Administration recommends a genetic test before using are listed in the table.


Genetic factor


Atomoxetine HCI (Strattera)

treatment of hyperactivity and attention deficit disorder

patients with a specific mutation in the gene of the liver enzyme CYP2D6 may develop serious liver damage

Clopidogrel (Plavix)

prevents myocardial infarction by suppressing the formation of blood clots

a variation of the gene of the liver enzyme CYP2C19 affects the metabolism of the drug, radically reducing its effectiveness

Cetuximab (Erbitux)
and Panitumumab
Panitumumab (Vectibix)

treatment of colon and rectal cancer

the drugs are effective only against tumors with a normal variant of the KRAS gene

Gefitinib (Iressa)

treatment of lung cancer

it is most effective in the treatment of tumors with a mutation of the EGFR gene

Irinotecan (Camptosar)

treatment of colon and rectal cancer

causes severe side effects in people with a certain genetic variant due to their lack of a number of liver enzymes

Tamoxifen (Nolvadex)

breast cancer treatment

variations of the gene of the liver enzyme CYP2D6 cause too rapid metabolism of the drug or the inability of its cleavage in the liver

Warfarin (Coumadin)

blood thinning

in patients with one of two or both specific genetic variations, the drug can cause profuse bleeding. Genetic testing allows you to choose the optimal dosage.

Perhaps in the near future, in order to analyze genetic variations that determine the nature of the body's response to a particular drug, patients will not have to send samples by mail and wait for the result for weeks. This will be possible thanks to the Verigene test system developed by Nanosphere, which allows you to analyze the DNA contained in a sample of blood or other biological material for the presence of one or more of the desired genetic variations within a few hours right in the doctor's office.

A. A disposable cartridge, inside which chemical reactions occur that ensure the isolation of DNA and the identification of specific genetic traits.
At the end of the process, the upper part of the cartridge is compressed, opening the slide with the sample prepared for further processing.
B. The barcode printed on the cartridge and the slide inside it minimizes the likelihood of accidental errors.
C. Reagent wells contain reagents necessary for the course of chemical reactions. After DNA isolation, they are released inside the cartridge using air pressure and mechanical valves. The desired DNA sequences are attached to the surface of the slide and the gold nanoparticles providing visualization of the result with the help of DNA fragments complementary to them. After that, the cartridge washes the unbound DNA fragments and nanoparticles and triggers a reaction, as a result of which the bound gold nanoparticles are coated with silver to facilitate scanning.
D. A hole for loading the cartridge containing the sample into the device, inside which the DNA is split into small fragments and separate complementary chains, which are subsequently attached to the slide.
E. A slide to which the desired DNA fragments are attached, labeled with gold nanoparticles coated with a layer of silver. A special device reads the results by evaluating the scattering pattern of the light beam incident on the sample.

Interpretation of the information encoded in DNA is still an extremely difficult task, and experts still know too little about the impact of various genetic variations on human health. However, this does not weaken people's interest in genomics, and many are already living dreams of the time when personalized medicine will finally fully come into its own and genome sequencing will become a routine medical test, which immediately after birth will allow each person to maximize the quality and duration of their life.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of TechnologyReview: Briefing: Personalized Medicine04.03.2010

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