“If a person has a serious illness, it is not so important for him that his data is depersonalized”
- Why do scientists?
- For example, when something is not diagnosed, the collectiongenetic material is absolutely necessary. To understand the state of the entire population, it is important to determine what the problem is for a particular sick person. We have about 20,000 genes, therefore, given all the possible variations, it is necessary to correlate them with the entire population. Storage can indeed be a problem due to personal data, but when they are anonymized, it is no longer possible to go back to the identification of genetic materials. And if a person has a serious illness, it is not so important for him that his data is depersonalized.
The cost of creating a national DNA center, inwhich the genetic samples of 80 million citizens should be stored, the Chinese government estimated at $ 900 million in 2017. After its creation, the DNA center will be engaged in population genetics, the study of the brain of infants and cognitive development, new cancer treatments, as well as rare and chronic diseases.
- How accurate is the next-genome sequencing method? Since this is an analog data collection method, should a percentage of errors be present?
- The percentage of errors is always there. The most common sequencing method is exome sequencing, when only 1% of the genome is examined. However, if you do not work with the entire genome as a whole, you cannot find out if you saw everything. There is one that is not visible at the genome level - for example, an epigenome.
There are things about which nothing is yet known. We do not pretend that we understand everything and that sequencing is the last word and the final solution to genomics.
Sequencing- the general name of the methods by whichthe sequence of nucleotides in DNA is established. First, the DNA molecule is cloned many times, then cut into several parts in random places and each section is studied separately. The difference between the methods is in exactly how the cut sections are studied.
Epigenetics- the science that studies changes in genes not related towith a change in the DNA sequence. It explains how the environment influences the activation or suppression of certain genetic traits. For example, voles born in the fall have thicker fur than those born in the spring, which helps them adapt to cold weather. Changing your lifestyle triggers biochemical reactions that also help change the properties of the body and, in the long term, prolong life.
“Transparency is important for reproductive health clinics”
- Is it possible to draw conclusions about the predisposition of the fetus to cystic fibrosis, cancer or orphan diseases in the early stages of pregnancy?
— In many clinics, for example, in BostonChildren's Hospital makes such conclusions from a scan, which shows whether the fetus has problems. This is an examination when, using different technologies, the embryo can be examined from different angles and diseases can be diagnosed.
Photo: “Healthy Moscow”
- Is it possible to identify a disease by genetic analysis until it occurs, slow down or eradicate it completely?
- Yes, at the level of family planning, parents are already“Remove” the most serious diseases that they have in their family. It is possible to suppress some states before they manifest. When I was doing gene sequencing for myself, the first thing I looked at was whether there was a possibility of amyotrophic lateral sclerosis to understand if my life span was long. It’s such a disease when you have paralysis and a brain failure.
Amyotrophic lateral sclerosis- progressive incurable degenerativea disease of the central nervous system that affects both the upper (motor cortex) and lower (anterior horn of the spinal cord and cranial nerve nuclei) motor neurons. It is a rare disease, the number of cases is estimated in the range of 2–7 cases per 100 thousand people per year. The average life expectancy with this disease is 5–7 years. But, for example, the famous scientist Stephen Hawking lived 55 years after his diagnosis. Since 1997, a wheelchair was designed for him, which he controlled using the only facial muscle that retained mobility. Communicated using a speech synthesizer. Despite his disability, Hawking continued to engage in scientific activities. He studied black holes, wrote several scientific papers and popular science books, traveled a lot, acted in films and even flew in zero gravity on an airplane.
- What would you recommend to a woman who has a very high risk of having a baby with poor health or incurable diseases?
- First of all, go to the clinicreproductive health, so that a personalized treatment plan is developed and prescribed for her and act accordingly. Also for clinics, such an aspect as transparency and honesty is very important: that they clearly state the percentage of success and the chances of recovery and conception of a healthy child that really exist. And if they cannot do something, then they must find a doctor who can.
Medical abortions are allowed in Russiaindications for up to 22 weeks. This is done if the mother has serious illnesses and the pregnancy threatens her life or the woman cannot fully care for the child. Serious abnormalities of the fetus are also grounds for medical abortion. A complete list of diseases is listed in the order of the Ministry of Health of 2007 "On approval of the list of medical indications for artificial termination of pregnancy." Among them are tuberculosis, heart defects, severe pathologies of the liver and kidneys, severe mental disorders, chromosome disorders in a child, and others. The question of the need for medical abortion is considered by an expert commission, which includes a woman-observing gynecologist, the head physician of the medical institution and narrow specialists in the disease that served as the basis for the abortion.
- Suppose, the test results showed in the newborn the presence of more than 200 genes that cause ophthalmic problems. What should parents do in this case?
- To give the right answer, a lot is neededdetails. After all, sequencing is a big problem, you get information and do not understand what to do with it. And sometimes such information that it would be better if they did not know. There may be different options. Sometimes it’s some kind of bad news that can be stopped by prescribing certain additives that reduce the risk of diseases, and sometimes such that you simply don’t know what to do with them.
“It happens that one small change affects the whole body”
- If we talk about mutations and mitochondrial DNA, why are there mutations that change the whole body or do not cause negative consequences at all?
- Research in this area, we andare engaged. It happens that some kind of mutation occurs and suddenly affects a part of the body where it should not be present at all. This is a huge question, for which there is no answer yet.
Photo: Healthy Moscow
“But what exactly underlies mitochondrial diseases, and how can mutations of individual cells cause damage to the body as a whole?”
- It happens that one small change affects the wholethe body. It seems that this is just one mutation, and it kills a person at a very young age. As for mitochondrial DNA, a patient may have only one disorder, but it causes a disease from which he dies. We conduct research and compare cell changes in humans, monkeys and insects. And so far, the absolute minimum has not been revealed, which, having changed, affects the whole organism as a whole and causes its dysfunction.
Mitochondria- cellular organelles that oxidize organic compounds and use the released energy.
Mitochondrial Disease- a group of hereditary diseases associated withdisruption of mitochondria. They stop producing energy, causing the cell to no longer perform its functions. The cells most affected in this case are the brain, skeletal muscles, kidneys, heart, liver, respiratory organs and endocrine system.
In 15% of cases the cause of the disease isa mutation in mitochondrial DNA (mtDNA), resulting in impaired mitochondrial function. Other causes of mitochondrial diseases include mutations of genes in nuclear DNA, the products of which are involved in mitochondrial metabolism. In total, mitochondrial DNA makes up no more than 0.5% of the total amount of DNA in the body. Mitochondrial DNA is a circular chromosome with a length of 16,569 nucleotide pairs.
A feature of mitochondrial diseases,due to mtDNA mutations, is the maternal type of inheritance (normally, mitochondria are transmitted only through the egg). Currently, more than 250 point mutations of mtDNA have been identified, as well as many different deletions (loss of a chromosome site) and rearrangements of mtDNA (the appearance of additional sites, rotation of a chromosome site 180 °, transfer of one chromosome site to another). More than 200 diseases caused by these mutations are known. Moreover, a mutation in the same mtDNA gene in different people can manifest itself to varying degrees, up to the complete absence of clinical manifestations. In this regard, the frequency of mitochondrial diseases is only 1-2 per 10,000 people, although mtDNA mutations can be detected in about 1 out of 200 cases.
"Scientists will not allow anything bad"
- How much do doctors themselves today trust in the results of genetic testing?
- For 10 years of work as a geneticist, I see that doctorsnow much more responsive to gene analysis. Previously, like everything new, this was suspicious, doctors denied the diagnosis, and now therapists are very happy to work with us. Of course, there are some doctors who are not open to this, but over time it will go away. Because genetic testing has certain advantages - higher accuracy and pharmacogenomics.
— Recently, the leadership of Russiaspeak outconcerns about the collection of genetic analysis of biomaterials of our citizens. Is there a real threat to the people whose data was collected and used by scientists?
“The thing is how this data is handled.” But I am sure that the Russian government and scientists will not allow anything bad. The good outweighs the bad, and the benefits are much greater. If we are talking about some very serious illness, then the question no longer arises, because the risk is minimal in comparison with the benefit.
- Is it possible to say that gene therapy is cheaper for the patient, and most importantly, it is more effective than the development of traditional drugs, at least in terms of orphan diseases?
- I can’t say for sure. For example, in the Boston Clinic, children are being treated, and it goes very well with such specific disorders, where gene therapy is really the best way. But medicine still needs to be developed before it becomes the main method.
According to the Ministry of Health, the treatment of orphan diseasescosts for patients from 100 thousand to several million rubles per month. The cost of one of the most expensive gene preparations of Lucsturn is $ 850 thousand. It is designed to treat Leber's amaurosis, a serious eye disease in which the protein necessary for the retina ceases to be produced, which leads to blindness. The final cost of the drug depends on the effectiveness of the treatment. According to the manufacturer, the drug is effective in 90% of cases. Prior to this, doctors recommended only supportive therapy - taking vitamins and intraocular injections, but these methods were ineffective: almost 95% of patients completely lose their ability to see by 10 years.
- A bit of science fiction: today you can adjust the healthy genome to get superpowers?
- Not yet. Someday it will be possible. I think that what everyone dreams about is the ability to change ligaments and muscles for more active movement.
- How will gene therapy and genetics develop in the future?
- I think that the diagnosis will be done on everythingearlier stage. And we will begin to identify situations where, for example, you can enter the virus that shows the missing protein. Perhaps this will not work for all diagnoses, but the range of application of gene therapy will gradually expand.