Cellular technologies in Russia: is the point of no return passed?

"We are 15-20 years behind"

Andrey Sobolevsky, SB RAS

Biomedicine is now called the number one scientific direction. Both in the world and in Russia. On the one hand, we have breakthrough results. On the other hand, to put it mildly, we are far from world leadership.

What prevents us from increasing the pace of progress towards artificially grown organs and 150-year-old healthy people, our correspondent was told by the head of the Laboratory of Epigenetics of Development of the Institute of Cytology and Genetics of the SB RAS, Doctor of Biological Sciences, Professor Suren Minasovich Zakiyan.

– In today's world, research in the field of cellular technologies focused on medicine is developing widely and rapidly. In our country, they are fragmentary: there are a number of strong laboratories in some institutes, and that's all. Now, first of all, we need to conduct screening, review everything that is being done in this direction in Russia. But it is clear that the backlog is gigantic. All the main events take place already in the beginning of the 21st century. Not so long ago, the first experience of working with stem cells was obtained. Doctors have hope for the rapid development of regenerative technologies, for the treatment of diseases that do not respond to conventional therapy. But everything turned out to be not so straightforward, and the signs that at one time were full of signs "healing with embryonic cells" belonged, as a rule, to artfully disguised charlatans. In fact, the discovery of induced stem cells by Yamanaka in 2006 was revolutionary. The Japanese scientist and his British colleague Gurdon were awarded the Nobel Prize in 2012, but over the past 8 years, so many new works have been published that, in my opinion, some of them will also bring their authors the Nobel.

In the last few years, the latest methods of genome editing have appeared – these are the TALENs (Transcription – Activator Like Effector Nucleases) and CRISPR(Clustered Regulatory Interspaced Short Palindromic Repeats)/Cas9 systems. They have already proven themselves to be effective and reliable genomic engineering tools. In 2011, the processes of high-precision genome editing, among which was the TALENs system, were named the method of the year by the journal Nature Methods. I am sure that its authors will also be awarded the Nobel Prize.

– You're talking about the backlog. What exactly does it manifest itself in?

– One of the symptoms of Russia's lag is the fact that the federal Law on the use of cellular technologies has not yet been adopted. Its draft was prepared, reviewed by a wide range of specialists and scientists, and the matter ended with the fact that the document was sent by the Government of the Russian Federation for further revision and can be adopted, at the earliest, in 2016. This looks sad, especially in comparison with how quickly the notorious FZ-253 on the reform of the Russian Academy of Sciences passed all the instances. But it is precisely in terms of cellular technologies that we have already lagged behind by about 15-20 years and, worst of all, this distance is increasing literally every day. I would even say every hour. In 5-6 years, Americans and Europeans will reach the threshold of a new breakthrough. And not only them. Conditions are being created in China that motivate Chinese scientists working abroad to return home. And it is not necessary to explain our lag by the economic crisis. Firstly, it has been developing and growing for more than one year, and secondly, any developed country comes out of the depression due to high technologies.

At the same time, the International Society for Stem Cell Research (ISSR) is concerned about the spread of suspicious or even frankly fraudulent methods of treating serious diseases in which cell technologies are allegedly used. The journal Cell Stem Cell published an article by Canadian scientist Timothy Caulfield, who believes that such methods are most actively advertised by medical institutions in China, Thailand, India and Russia. In these countries, stem cells are offered to treat such serious diseases as Parkinson's disease, autism, spinal cord injuries, and so on. As a rule, advertisements and clinic websites do not provide detailed information about the essence of the treatment methods used. But it is quite obvious that serious studies to assess their effectiveness and safety have never been conducted.

– What do you see as the reason that Russia is not among the leaders?

– The key problem is the inequality of opportunities. We have excellent researchers, talented young guys. When I talk to my Western colleagues, I am convinced that we think the same way. But there is a gap between us in financing, equipment, and many other things. A small example: we are forced to order imported reagents not directly, but from Russian distributors, and the price of one item increases up to 300 percent! And delivery lasts on average at least three months after prepayment. American and European colleagues receive their orders every other day.

And secondly, our youth are not socially protected. The scholarship of a postgraduate student is 2500 rubles, and in Europe 1500 euros, there used to be postgraduate dormitories, now there are problems with the availability of beds. Graduates of the best Russian universities, postgraduates and researchers are in demand in the West: it turns out that we train specialists for other countries. The training of one student costs about 20 million rubles – these are the losses we bear, what kind of leadership can we talk about?!

– Unfortunately, today we take it for granted. But is it possible, in unfavorable conditions, to single out some main direction in order to focus on it?

– In recent years, activities in the field of cell biology have been significantly strengthened by new developments and methods of genetic and genomic engineering. TALENs and CRISPR/Cas systems allow manipulating the genomes of living cells and whole organisms of model animals and humans. In particular, with the help of these technologies, it became possible to correct gene mutations in pluripotent cells. Cells with an altered genotype can be used for the therapy of incurable hereditary diseases with a monogenic nature. We are close to producing cells resistant to viruses, such as HIV. In addition, with the help of these systems, it is possible to build cellular models of hereditary diseases that have a huge potential for use in pharmacology, at the preclinical stages of testing new drugs.

This is a very important direction. We have learned to model the disease at the level of cells, not organisms. The methods of genomic editing have been mastered in our laboratory, a biobank of cell lines of hereditary pathologies has been created. Special attention is paid to neurodegenerative and cardiovascular diseases. Metaphorically speaking, we already have "patients in a Petri dish" on whom we can screen medicines. This entails a number of advantages compared to animal experiments. With proper development – and, above all, serious state support – of these areas in Russia, it is quite possible in the near future to reduce mortality and disability of the population for various groups of diseases.

– Don't you think it's a paradox that with Russia's indisputable lag in the development of biomedicine, world-class results have been achieved at SB RAS, as we have repeatedly reported?

– Yes, the Siberian branch has a number of remarkable developments. But mostly they are of a fundamental nature, at best we can talk about the foundations of future technologies. In fact, there is no translational system in Russia, within the framework of which clinical trials are conducted according to strict international standards, multiplication and adaptation of scientific methods to practical medicine are carried out. For us, this system is partly replaced by international partnerships (as an example, I will give the Japanese pharmaceutical corporation Takeda, with which the SB RAS has concluded an agreement), but this is all very fragmentary. My laboratory has, for example, a biobank of frozen cell lines carrying hereditary diseases, but the next stage of research is the search and selection of new drugs, which requires cooperation with the involvement of leading specialists on the basis of specialized research institutes of the SB RAS, RAS, RAMS, or the creation of new research structures.

– Do scientists, in addition to establishing direct contacts among themselves, put forward any additional initiatives for the development of biomedical direction in the country?

– In December 2013, a very representative congress on regenerative medicine was held in Moscow, where it was decided to hold symposiums with sufficient frequency, at which it would be possible to share the latest results in this field. The first of them, "The latest methods of cellular technologies in medicine", will be held in Novosibirsk Akademgorodok in the first days of this September. Plenary and poster sessions, round tables, as well as the adoption of the final memorandum on the need to create cellular technology centers in Russia are planned.

There is no doubt that such a huge region as Siberia should have its own Center of such a profile in order to intensify research – both of a fundamental nature and on tasks that will find an outlet in experimental and clinical medicine. Novosibirsk Akademgorodok has a huge potential. There are a number of research institutes conducting research in the field of cytology, genetics, molecular biology, biochemistry, fundamental and clinical medicine. Akademgorodok is home to one of the leading universities in Russia – NSU, which trains first-class personnel in biological and medical specialties. Of course, this is the optimal place for the organization of the Siberian Center for New Cellular Technologies. Special attention should be paid to work with induced human stem cells, which have a number of undoubted advantages over embryonic ones and enormous prospects for practical use.

The tasks of the Center should also include training personnel for research institutes of the integrated system of the SB RAS and SB RAMS, medical staff and doctors who own new cellular technologies. Within the framework of the future Center, it is necessary to create a Consortium on Cellular Technologies to coordinate work with the involvement of leading specialists on the basis of specialized research institutes of the Russian Academy of Medical Sciences: cardiology, neurology, oncology, hematology, pharmacology, endocrinology, traumatology and other specialties.

In order to change the critical situation developing in our country, the organization of the Center for Cellular Technologies must begin today, and there are all the prerequisites for this. Procrastination will lead to Russia lagging behind the world level for the next 15-20 years, which may make it insurmountable.

Portal "Eternal youth" http://vechnayamolodost.ru17.04.2014