Postgenomic biotechnologies
New generation chemotherapy — without hair loss and yellowing of the skin
It included officials of the Ministry, scientists from the Russian Academy of Sciences and the Russian Academy of Medical Sciences, representatives of industry business. A competition was announced for the development of a strategy for the development of the pharmaceutical market until 2020, the winners were determined, and at the moment the concept has been developed and submitted to the government for coordination with ministries and departments. At the same time, the Academy of Sciences is working to create an infrastructure that will make it possible to implement the goals of the future strategy as efficiently as possible. One of the resource centers was the Department of Postgenomic Biotechnology of the N.I. Vavilov Institute of General Genetics of the Russian Academy of Sciences.
Its head, a member of the expert council on the biotechnological and pharmaceutical industry of the Committee on Industry of the State Duma of the Russian Federation, Doctor of Biological Sciences, Professor Valery Nikolaevich Danilenko, told STRF about the promising developments of his employees in the field of creating new medicines.
"Postgenomic" is identical to "postindustrial"
Your department is called "postgenomic biotechnology". Why post genomic?— We live in an era when the sequences of the human genome have been sequenced and determined, hundreds of genomes of microorganisms — useful and harmful - have been deciphered.
Until the early 90s, the creation of drugs was largely empirical. Now the process has moved to a completely different level: medicines can be created faster and more accurately using the entire body of knowledge. If you have access to the database, it doesn't matter where you are. With the appropriate equipment and competencies, medicines can be made anywhere. This is accessibility associated with the globalization of science. The scientific process is now directed, concrete, and not empirical. In this sense, the word "postgenomic" is identical to the word "postindustrial".
What are the tasks facing the department?— The pharmaceutical industry development program assumes that about 200 domestic medicines should be created by 2020.
Several dozen of them should be innovative means of a new generation — "targeted" drugs, targeted drugs (from the English target — target).
The creation of such drugs is the main task of the Department of Postgenomic Biotechnologies, which was established at the Institute of General Genetics of the Russian Academy of Sciences two years ago. First of all, we are talking about the creation of medicines to combat socially significant diseases, which include heart disease, cancer, tuberculosis, diseases associated with nosocomial infections caused by streptococci, pseudomonads and other microorganisms. These microbes are resistant to most existing antibiotics. In our department, we create drugs to which resistance does not arise.
Which laboratories are included in your department?— Firstly, the laboratory of microbial genetics, whose employees are engaged in the search and structural and functional validation of new biomishens for the creation of anti-infectious drugs.
It also conducts research and the creation of bacterial test systems for rapid screening and search for anti-cancer drugs, based on both human and bacterial genes. It is biomishen and test systems for screening that are now being evaluated as the most effective techniques for reducing the cost and reducing the time to create new drugs.
The second laboratory studies human stem cells and applies the technologies being developed for various purposes, including using stem cells to regenerate certain human tissues. In terms of search, this is a separate important area, which is at a fairly high level in Russia. In this laboratory, we are creating new test systems based on stem cells for screening various drugs. These are the listed anti-cancer drugs, and drugs of cardiological action, and neurological action.
The third laboratory is engaged in the study of genetic diversity in the insect world. It would seem that absolutely fundamental research, but they also have applied significance. We use such model insects as drosophila or a common cockroach to search for biomishens and create test systems for screening new drugs so that it is possible to pass the stages before their testing on mammals and humans cheaply and quickly. Laboratory scientists are studying why cockroaches develop resistance to most insecticides, since we are engaged in the creation of drugs not only for medical purposes, but also intended for pest control.
Now we are forming a fourth laboratory — probiotic microorganisms. She will be engaged in obligate human microflora, that is, the creation of preventive means to increase immunity in cases of problems associated with dysbiosis caused by the use of many antibiotics, stress conditions and other factors. We are conducting fundamental research in this area.
What has already been done in the two years of the department's existence?— Two years ago, we became participants in a major European project "Creation of protein kinase inhibitors, new anti-cancer and other drugs in the post-genomic era".
The project involves 32 laboratories from 16 European countries, including France, England, Italy, Finland and Russia. Interaction with other teams within the framework of this program helped us a lot in the formation of the department. We were able to create several drugs that could potentially be used as anti—cancer - inhibitors of Aurora protein kinases, PIM, CDK. In total, there are 450 protein kinases in the human body, each of them is tied to some kind of disorders and diseases, in this case, the listed protein kinases are associated with the most important diseases - leukemia, prostate and breast cancer. For almost every one of these diseases, we have certain substances that can be candidates for drugs for their treatment.
Also in the field of breakthrough and fundamentally new drugs, inhibitors of bacterial protein kinases, inhibitors of virulence factors of tuberculosis and other infectious diseases have been developed. This is the success of Russian science, because we were able to create original test systems for screening bacterial protein kinases. Virulence factor inhibitors do not kill mycobacteria, staphylococci, streptococci and other pathogenic bacteria that initiate inflammatory and other pathological processes in humans, but by acting on these bacteria, block the manifestation of their pathogenic properties. It is known that most people (at least 90%) are carriers of microbacterium tuberculosis, but do not suffer from it. Those who have a weakened immune system are ill, who are often subject to stressful situations, etc. Our drugs allow you to remove pathogenicity, while there is no resistance to them. It is the problem of antibiotic resistance that has forced many pharmaceutical companies in the last five to eight years to stop producing antibiotics and leave this area, shifting the responsibility to the state because of the high cost and inefficiency of the competitive race. Fundamentally new medicines were needed, and we reached the level of their creation.
Russia has every chance to become a leader in drug development
Targeted drugs are not new on the world market. There is already a lot of competition in this segment. How do you assess the prospects for promoting domestic medicines?— Yes, it is.
For example, over the past few years, several new so-called "biomishen-directed" anticancer drugs have entered the world market, including the Russian one. It would seem good — we will buy them. But, unfortunately, there are dozens, if not hundreds, of forms of oncological diseases, each of them requires its own drug, its own method of treatment. That is, demand still significantly exceeds supply.
The drugs on sale are blockbusters that are used everywhere against a number of the most common forms of cancer. And these are very expensive medicines. One of these imported drugs was bought in Russia alone last year for hundreds of millions of dollars, despite the fact that our entire pharmaceutical market is about 15 billion.
The creation of such drugs and their introduction to the market are associated with huge costs — both financial and temporary (the usual terms are from 10 to 12 years), but the development of "biomishen—directed" drugs is, without a doubt, very promising. I will say more: Russia has every chance to be at the forefront in this technological direction of combating the most complex diseases of mankind.
What does the scheme of creating and entering the market of a drug look like?— We give the task to chemists to synthesize certain groups of substances with certain properties.
Then our colleagues, specialists in the field of bioinformatics, test these substances on computer programs (this stage is called computer design or docking), then select those that are most effective. Then we, biologists, test these substances on specific molecules on biomishens. Then we determine the fact of the directed action and already in the clinic — in our case, in the Russian Cancer Research Center — there is a check on cancer cell lines — there are about 50 of them. They are tested for efficacy, cytostaticity and cytotoxicity.
We have already carried out our developments through this whole system and have drugs that have a specific effect — original patentable molecules that act on certain cancer cell lines.
Now we are approaching experiments on mice. At this stage, the so—called semi-lethal dose is tested, which kills half of the animals that are injected - thus toxicity is tested. This is part of the preclinical testing. Having completed the "pre-clinic" on animals, we proceed to the clinic. The second stage and the third — in public. Actually, we can talk about the drug when the first part of the tests (on mice) has already been completed. Then it becomes interesting for pharmaceutical companies that manufacture medicines.
Is it already possible to talk about the specific advantages of new drugs in comparison with the ones used?— Many anti-cancer drugs used so far are very toxic.
As a result of treatment, for example, baldness occurs. Our developments are hundreds of times less toxic, while the therapeutic effect is directed not against all forms of cancer, but against specific ones. And our drugs are very effective. This is a new generation of chemotherapy — cancer treatment without hair loss, yellowing of the skin and other unpleasant consequences.
We expect the main financial support within the framework of Pharma 2020
Advanced technologies require no less advanced equipment. Usually academic institutions complain about outdated devices and the inability to update the material base. Is this problem relevant to you?— Yes, of course.
At the Institute of General Genetics three years ago there was a crisis caused by the lack of equipment. In the last two or three years, small growth centers have appeared in many academic institutions. This happened thanks to the creation of collective use centers and major projects supported by Rosnauka.
In 2007, we received a set of microscopes that can be used to create drugs in the field of "nano", in the amount of 800 thousand dollars. Next year we are buying a robot for screening new drugs. This is a modern robot worth about 300 thousand dollars. Of course, this does not exhaust our needs, but we can work much more efficiently.
Do the main funds come through the RAS? Or do you have to attract other sources of funding?— What goes through the Academy of Sciences is clearly not enough.
After all, there is a distribution — "all sisters on earrings." We expect to receive the main funding not from the RAS, although we hope for this source too. The main funds should be received from the Ministry of Industry and Trade of the Russian Federation within the framework of the pharmaceutical industry development program. In the second place — from Rosnauki through the Federal Target Program "Research and Development" in terms of program activities "Living Systems".
We hope that the ministries will also help us in training personnel. On the basis of the Institute, together with the Department of Genetics of Moscow State University, an educational research center has been created. In order for it to function properly, money is also needed.
Are drug manufacturers in no hurry to fund research and development?— Business?!
You have touched upon one of the most important problems. We do not have the so-called big pharma, that is, large pharmaceutical companies, the end consumer of our scientific developments, who will conduct their clinical trials and market introduction.
This is the main task of the state — the creation of several large pharmaceutical corporations on the basis of public-private partnership. As far as I know, some decisions in this direction should be taken by the end of this year. The development strategy of the pharmaceutical industry is primarily a business.Is the pharmaceutical business that already exists ready to cooperate?
— Unfortunately, our business traditionally prefers the following position: give us the funding that is allocated for scientific research, and we will develop everything ourselves.
Business can be understood, it's easier for him. But the task is beyond the power of those pharmaceutical companies that we have.
How do you solve the personnel problem? After all, this is almost the main obstacle in science now. Young specialists go abroad, old ones retire…— The problem of personnel, of course, has not been solved here — both within the department and within the institute as a whole.
This is a complex problem. And, unfortunately, everything is very neglected — some even believe that the process is irreversible.
But in fact, not everything is so bad. Here we have launched a project on probiotics, the institute has become the parent organization this year. The amount of financing of the project is 115 million rubles for two and a half years. A senior researcher at the Academy of Sciences today receives 18 thousand rubles, this is the base rate. And within the framework of the project, he has the opportunity to receive another 28 thousand rubles.
I needed three employees, we advertised, 10 people responded. Here is such a competition!
From your point of view, what are the most relevant risks to the development of domestic pharmaceuticals and the creation of new domestic drugs?— The main danger is the financial crisis.
Its further deployment may mean the suspension of existing projects and programs, the curtailment of global strategic plans for medicine, healthcare and pharmaceuticals. After all, everything is largely tied to the opportunities of investors. I would like to avoid this.
Corruption and disunity in the actions of various departments and organizations in the implementation of major goals and objectives are also frightening. Each department has its own programs and projects that it implements due to its understanding: the Ministry of Science is one, the Ministry of Health is another, the Ministry of Industry is the third. And there is almost no coordination. There are groups of business and near-scientific people who are admitted to these programs. Others simply do not have the opportunity to participate — no matter what results and abilities they possess. And this is also a problem.
In general, there are reasons for pragmatic optimism. Compared to the difficult situation of the "Zurab time", when it was officially proclaimed that we do not need new medicines, the approaches of officials are changing for the better.
Well, we, scientists, did not sit idly by, we worked, convinced and were able to convince the state that the development of domestic pharmaceuticals is necessary.
Portal "Eternal youth" www.vechnayamolodost.ru28.10.2008