Personal medicine

The editors of the "Attic" figured out that,
what is personalized medicine?

Alexey Tymoshenko

The words "personalized medicine" have been found regularly lately, as well as "genome analysis". But what is behind it is not always clear. The editors of the Attic talked with Sergey Moshkovsky, head of the Department of Personalized Medicine at the Moscow Institute of Biomedical Chemistry.

– What is personalized medicine?

– This concept includes several aspects. Firstly, it is an individual selection of drugs taking into account the individual characteristics of the body. A classic example: in developed countries, a special genetic test is carried out that determines the metabolic rate. For example, many people from Africa should receive a smaller dose of certain medications, because they have a less active metabolism than Europeans. This is an example of personalization at the level of race, there is also a more subtle one. There are other aspects of personalized medicine.

– Predispositions to diseases?

– Not only that. You can, for example, predict sports success. There are variants of genes in which a person most likely will not become an Olympic cycling champion, but he will ruin his health in training. Although another athlete in the same conditions will turn into a world champion.

Personalization also includes cellular technologies, when, for example, a cancer vaccine is made based on the cells of the patient himself. And finally, these are personalized diagnostic and forecasting methods made for a specific patient.

– How realistic is it to create a biosensor that can diagnose not by blood from a vein or using biopsy material, but in some more convenient and painless way? For example, by exhaled air?

– In general, it is much more difficult to analyze air than liquids.

– Because it is necessary to distinguish the molecules that have fallen from the lung tissue from the molecules of the recently eaten shawarma?

– Yes, exactly. There's dust, flakes of skin. However, scientists have ideas of what can be done. You can take a filter, ask a person to breathe into it, then collect all the material and conduct a targeted PCR (polymerase chain reaction, search for a given sequence of DNA nucleotides; with its help, for example, you can search for fragments of cancer cell genomes – approx. "Attic").

– And then we won't confuse human cells with cat hairs?

– No, we will not confuse it, we will be looking for a cancer genome, no worm or cat has such a Badger. But, I emphasize, this is still all at the level of ideas. Now there is such a topic in the diagnosis of cancer, it is in the process of development. So far, there is only a diagnosis of cancer of the rectum and colon by fecal analysis, in which a given DNA is searched, this method has passed the first clinical trials. And feces is a very dirty substance in all respects, there are a lot of different bacteria with their DNA.

– And what can be diagnosed with DNA at all?

– It is possible to diagnose hereditary diseases and cancer, predict sports achievements, determine the tolerability and effectiveness of drugs, for example, warfarin. It is possible to conduct a metagenomic analysis (a metagenome is a set of genomes of symbiont bacteria, intestinal microflora - approx. "Attic") and even pick up a diet. However, the selection of a diet and the identification of predispositions to diseases still exist at the level of general recommendations for prevention.

– About diagnostics in general. How reliable are the DNA tests that you can buy by mail? Are these recommendations somehow different from the banal "you don't need to smoke because it causes cancer"?

– There is another problem with predisposition. Suppose you have five thousand sick people and five thousand healthy people. In the group of healthy people, one person has the "letter" A in a certain place of DNA, and in the group of patients, the "letter" A in this place is already found in 50 people. It seems that this is a big difference, but its clinical significance is limited: despite the fact that in patients the "letter" A occurs 50 times more often, in fact 99 percent of people from this group have another "letter" in the same place of DNA, not A. That is, despite the difference, it is impossible to say, that the presence of A in this place definitely allows you to identify the disease.

Two people may have almost the same DNA, but the first patient will have one nucleotide in one place,
and the second one has another one. Illustration: David Eccles / Wikimedia

– Today there are companies on the market that claim to be engaged in personalized medicine. They send customers a set for taking a DNA sample, analyze the samples sent and report: "Your probability of such and such a disease is increased by so many percent." So what they're doing is useless?

– Not at all. Even if this is not absolutely reliable and medical information, but it is interesting. Here is the same story as, for example, with smartphones: these devices are useless for survival, my grandfather lived 85 years, he did not have a smartphone, but he lived a full and fulfilling life. However, our life is more interesting with gadgets, so I would not pass off the manufacturers of such tests as charlatans on a par with fortune tellers and clairvoyants.

– And what is the accuracy of different types of molecular diagnostics in general?

– Accuracy can reach 99%. But nevertheless, a test that gives such results may not be suitable for searching for cancer at an early stage in the entire population.

- why?

– Let's say we have a million people. Let a thousand have cancer – it usually occurs with about this frequency. The test has an accuracy of 99%: it seems to be very good, and the developers of such a technique will publish an article in a good magazine. With such accuracy, out of thousands of real patients, doctors will correctly find cancer in 990 people. But how many healthy people will mistakenly receive a preliminary diagnosis of "cancer" if this test is used en masse? With 99 percent accuracy, it will be one person out of a hundred. We subtract a thousand sick people from a million people, 999 thousand healthy people remain. If a false positive answer comes to every hundredth, we will get 9900 errors.

In other words, only one out of ten who received such a preliminary diagnosis is really sick. The rest will have to do a painful and expensive biopsy in vain, as well as hear the terrible "you probably have cancer." Someone, having heard such a thing, can hang himself. Insurance companies will also be very unhappy with the bills for unnecessary diagnostic procedures.

For traditional cancer diagnosis, it is often necessary to take a tissue sample,
which is associated with not the simplest, safest and painless procedures.
The video shows a thyroid biopsy without comments (VM).

About cancer– Why are you talking about the cancer genome separately?

As if it's not the genome of a person with a disease, but something special?

– The fact is that cancer cells are not human in some sense. Any cancer is the result of a mutation in cells, and we strive to find out in each case where these mutations occurred. Mutant cells already differ at the DNA level from those around them, and therefore they can be found. Another thing is that they are constantly changing, new mutations appear, and in general, cancer behaves like a bacterial infection, evolves and survives due to its increased ability to mutagenesis.

– Is that why the immune system can't cope with them?

- Yes. The immune system and medications. There are good drugs that can kill most of the cells, but some part survives and gives relapses. It's good that the medicine works, but it's bad that after a while, about a year, the disease returns.

– Is there a vaccine for cancer?

– Yes, there are vaccine preparations, and many of them are achievements of personalized medicine. They are made on the basis of the patient's own cells, lymphocytes are "trained" on tumor cells. The production of such drugs is very expensive, and, unfortunately, they work only in a small part of cases: 1-3 percent, depending on the type of tumor. Therefore, such vaccines are not widely used yet. It would be good to be able to predict, to choose those people for whom vaccination may be effective.

– Why did you decide to do such expensive and complex research in Russia, and not, for example, in the USA?

– In the USA it is easier with reagents and equipment, all this is more expensive here. We have problems with reforming academic institutions: we inherited a system that, if it was effective, was in the distant past. Even if a genius of Landau's level manages the reform of science, it is not a fact that he will find a solution to all problems. There are a lot of them, and they greatly complicate the work. But, nevertheless, I'm not leaving – probably because I'm used to working here. I'm in charge of the group here, there are young and talented people. They just need to throw money.

– And where do students come to you from?

– I myself am a professor of the Second Honey, RNIMU named after N.I. Pirogov, Faculty of Medicine and Biology. They come to us from the MSU biofactory, from the Physics Department, they are cool. Physicists are suitable for such work, in principle, but they only despise biology (laughs).

Portal "Eternal youth" http://vechnayamolodost.ru26.03.2015