Russian scientists have taught nanoparticles to count
"We have serious chances to overtake the whole world"
Russian scientist, having published an important work,
he told me about what prevented her from doing it fasterNikolay Podorvanyuk, "Newspaper.
Ru" about the problems of ordering and delivery of reagents, without which developments in the field of life sciences cannot do. In order not to miss the priority, he worked 70 hours a week, spent about $ 20 thousand of family money on reagents, and spent part of the experiments at home, since security did not allow him to work at the institute at night.
– What is the essence of your work published in Nature Nanotechnology?
– We have developed a method for turning any nano- or microparticle into a miniature "biorobot" capable of making decisions independently – for example, whether to interact with a cell. We have taught a particle to calculate any function from a functionally complete set of logical functions ("YES", "NO", "AND" and "OR") for two biomolecule operands. Now, for example, nanoparticles can deliver drugs to cells based on the analysis of several parameters at once. By the way, our method is the only one that can do without using DNA when calculating a complete set of logical functions.
The scheme of the nanobiocomputer from the article Biocomputing based on particle disassembly
– For the treatment of what diseases can your system be used?
– It is too early to talk about treatment, but for the treatment of diseases, our development is the basic brick in the foundation of the creation of fundamentally new, "smart" medicinal agents. To explain the possible potential of such agents for a wide audience, I will give very simplified examples. "Smart" agents could monitor blood composition and generate insulin when two conditions are met simultaneously: high sugar and low insulin levels (the result of the logical function "A and not B" is 1). As soon as the insulin level normalizes, the generation of insulin stops.
Another example is a blood clotting disorder. Unfortunately, many people have this problem...
– ...I immediately remembered Tsarevich Alexei, who was suffering from hemophilia…
– Well, this is an extreme case. For example, in the case of an increased risk of thrombosis, "smart" drugs could provide invaluable help by regulating the concentration of anticoagulation agents in the blood. Although their potential is certainly not limited to these two examples.
As for the use of the method for complex blood tests, this is probably already tomorrow, although this is already a matter of rapid business development, competition with other methods, etc.
– This is a rare case – a publication in such a prestigious journal as Nature Nanotechnology, made entirely by Russian authors. Have things really improved so much in Russian science in recent years?
– Of course, I am very lucky to have good colleagues. But I would like to emphasize that in the field of nanobioscience (in the good sense of "nano", and not in the sense in which this word is often used in our country), there are now a huge number of good ideas that lie literally on the surface, just haven't reached the hands in the West yet, and that a graduate student can almost implement not alone. It seems to me that this is a unique situation – a unique time with unique opportunities that cannot be missed.
We can really overtake the whole world in this area. But we have a big problem: the delivery of reagents to Russia is too long.
I specifically calculated: despite the fact that I worked an average of 70-80 hours a week with one day off per month, necessary so that attention would not be dulled during experiments, the work progressed about six times slower due to problems with the delivery of reagents than it could go if the reagents had I appeared as quickly as scientists in other countries. Six times is a lot in the modern scientific race.
– There are no domestic reagents at all?
– It should be understood that advanced science requires the use (I would even say it is based on the use) of extremely rare reagents. These reagents are rare either because they are needed by an extremely small number of researchers, or because of the secrets of know-how. Accordingly, each such reagent is often produced by only one or two firms in the world, and sometimes even by separate scientific laboratories that first received the substance and sell them to other scientists. And here Russia is not in any special position. For example, I know one very successful laboratory of ours that produces certain antibodies the best in the world, and the whole world actively buys these antibodies from this laboratory, though through a company in the EU.
In addition to such small firms, the world has a convenient system of several global manufacturers and suppliers that store and deliver a wide range of reagents for scientific research. They not only produce some substances, but also carry out the functions of distributors of many small manufacturing companies, which makes their products much more visible on the market.
The main problem is that if I order reagents through standard channels, as provided by the existing system in Russian science, it usually takes at least a month to deliver reagents – sometimes it takes three months. For me, the record is nine months.
That's how long I was waiting for the reagent available in the warehouses of the manufacturer. In addition, we are forced to overpay a lot to a Russian intermediary company that carries reagents from abroad, and at the same time it is not at all clear in what condition these expensive substances will be delivered. In particular, one day I had to order a reagent that loses its properties after two weeks if the temperature reaches plus 4. It should be stored at minus 70 and below. All Moscow intermediary firms said they would bring the reagent within 90 days. Question: in what condition will this reagent arrive? And if it doesn't work, it will be very difficult to understand what the reason is: did it deteriorate during transportation or is my scientific hypothesis not working?
– How did you solve these problems now, in the process of working on the current article?
– Of course, getting some basic reagents like NaCl (table salt) is not a problem at all, some reagents were already given to me by good people from our institute (IBH RAS) and INBI RAS at the final stage of work on the article, for which I am very grateful to them. But the vast majority of complex reagents, such as particles, proteins, etc., I bought for purely personal money and set up a delivery system that even DHL could envy. Delivery didn't take me longer than two weeks.
– What kind of system is this?
– The simplest case is when I went abroad for a conference myself. I then ordered reagents to my hotel, or to friends or colleagues at conferences, and brought them with me. Probably the most difficult combination is that when I arranged delivery to a friend in the USA, he transferred the delivered goods to another person in Europe, and he already brought them here.
The main problem with this method in the USA is that most large companies categorically do not send reagents to home or hotel addresses and require only legal addresses. At some point, I agreed that the reagents would be delivered to a friend of my friends in an IT company, to their legal address. I promised that they would bring two small test tubes of 1 ml each, and the company, without informing me, sent everything with dry ice (just in case). As a result, they brought two large containers in red duct tape and with all kinds of tags – "Fragile", "Perishable", etc. Colleagues then looked at my friend very askance.
At the moment, I feel like I've already strained, perhaps, all my friends. There is no one else to strain, so I will definitely not be able to organize such a system for the next publication, and there is no moral strength for such a thing.
– And in Russia, what are the problems with the delivery of reagents?
– The first is that our academic institutes do not undertake the purchase of reagents abroad, because they do not have specialists in working with customs. Surely there are other obstacles that I don't even know about, so all reagents are usually ordered through Russian intermediary firms. At the same time, there are already two real problems. One is that firms are waiting for a batch of orders to be organized so as not to drive a car from abroad with one test tube. As a result, they make purchases no more than once a month, on New Year's Eve – a little more often, there are more orders there, because everyone needs to have time to spend the money that came from the budget, so the cars are completed faster. Once a month is when it comes to purchasing from warehouses in Germany. If you try to buy reagents through them not from Germany and, in particular, from small firms, the standard delivery time is 90 days (although in reality this period may significantly increase). Another problem is the price increase in comparison with the prices of the same reagents abroad. The margin may be more than twice.
That is, we pay public money, which, in fact, goes to enrich dealers and does not serve science at all. In addition, of course, there are issues with customs. Since we work through resellers, we do not know how much the customs slows down the process.
– And how much, if it's not a secret, did your research cost?
– Well, if you don't count the salary and basic biochemical reagents like NaCl, etc., then I spent about $20 thousand on more complex reagents. And it was my and my family's money. No funds supported this work.
– I see. And what, in your opinion, should be done to improve the situation with the supply of reagents?
– I have a certain solution that I would like to propose. I decided to do the current research three years ago after talking with Dmitry Anatolyevich Medvedev. In 2010, I participated in the Zvorykin project. It was only then that the creation of Skolkovo was announced, and its winner was to become a resident. It was just announced about a separate fast customs for Skolkovo. I was very attracted to it, and I decided to participate in this competition. True, he did not become a winner, but he became a finalist. And six months later, I was honored to be invited to a meeting of the modernization commission on May 24, 2011 as a participant of the "round table" (as a young scientist). After the end of the official part and the broadcast, Dmitry Anatolyevich asked if anyone would like to add anything. Then I introduced myself (as a graduate student at MIPT) and told that there was such a problem with reagents. I was pleasantly surprised by the rather detailed discussion that followed between Medvedev, Sobyanin and other high-ranking officials.
– And what was the summary of this discussion?
– It was said that a separate customs office is being created at the Kurchatov Institute for scientific needs, and if it goes well, it will serve all other scientific institutions. But, according to my information, scientists from other institutes cannot use the services of this customs yet.
Actually, I understood then that this was one of the requests of thousands of people and thousands of scientists sent to the government. I understood that against the background of requests from leading scientists, the opinion of a graduate student is insignificant. There was a desire to strengthen my position by showing that my opinion may be of interest to the common cause. I have seen that recently almost all Russian experimental works in the field of life sciences, life science, published in the best journals with the highest impact factors, have somehow been done with the participation of those who work in the West. As a person who directly stands at the laboratory table and knows how to do some work with his hands (and before that I had work in such prestigious journals as PNAS and ACS Nano), I believe that the main problem in this area is just reagents. You can find money for work. But it is impossible to do work without reagents. So the idea arose to risk your time…
– ...and money…
– ...and many other things to show that if the problem with reagents is solved, then in Russia it is possible to carry out research at the forefront of world science entirely by Russian scientists. Here it is necessary to make a reservation. Of course, I actively support international cooperation in science. However, in all developed countries, publications are published, both with the participation of scientists from other countries, and made by scientists exclusively from this country. And in our country in recent years, the best journals in the field of life sciences have published articles only with foreign participation or affiliation. Although the pioneering work of professors Sergey and Konstantin Lukyanov and Dmitry Chudakov from IBH RAS, Sergey Nedospasov from IMB RAS and other outstanding scientists working in our country, of course, cause sincere admiration.
At that time, I had several interesting ideas spinning in my head, so I chose one of them and started working on it. I understood that the probability of success was low and the venture looked like an adventure, so I did not involve anyone in this venture until I was convinced that it was viable. At first, these studies were purely side activities relative to other responsibilities. Therefore, I had to work a lot: a 70-80-hour working week became the norm. Literally two weeks after the first experiments, I realized that if I had the opportunity to buy the necessary reagents, it would be possible to do all the work in two months, and it would only be necessary to write an article.
At some point, I was thinking for a week whether it would be worth it to go abroad for two months, do the work without having a headache with reagents, and publish it. But I decided that I was young, I could take a chance once and try to "change something".
I was afraid to order from here such reagents that I would ideally need for financial and logistical reasons. These were very expensive substances (about $2500 for one or two experiments). If they were ordered through standard channels with grant money, I would most likely have to wait 90 days to deliver them and try to see if my scientific hypothesis works, and then another 90 days to get them in sufficient quantity for thorough work. As a result, it would take six months before the start of real experiments. Therefore, we had to choose schemes for setting up experiments according to the probability of success / cheapness ratio. This, of course, negatively affected both the speed and the result. In the end, this approach forced me to show biocomputing with "uninteresting" model substances, that is, those that have no biomedical significance. I think, without losing priority, I had no chance to demonstrate the work of a method for tracking, say, diabetes. And I couldn't do it just because I was forced to work on cheap reagents. Accordingly, this greatly complicated the publication of this work.
At some point, in pursuit of available reagents, I had to work with a protease protein given to me (this protein eventually "crunches itself"). This protein has been stored since 1990 and during this time has already managed to "crack" itself significantly. I had to painfully come up with some methodology to try to see the signal from the remainder of the "unbroken" protein, despite the harmful signal of the "gnawed" one.
– What other problems did you encounter while working on the article?
– There was a period when I had to follow the experiment for about 20-24 hours continuously. But, for example, the Institute of General Physics (IOFRAN) has a very inconvenient system for working on weekends and after ten in the evening. At the Institute of Bioorganic Chemistry (IBH) at that time, the guards even threatened to take away the pass. Of course, it should be noted that IBH has very good management, I was very lucky to work there. As a result, the problem with night work was solved there. Another thing is that it took some time. But while the issue was being resolved, I had to put experiments at home so that the hardworking Chinese would not overtake.
– What kind of plan to solve the situation with reagents do you have?
– When I was working on the article, Yuri Milner had just established first the prize for fundamental physics, and then the prize for life sciences. And if Milner or our other patrons who support Russian science and education (Zimin, Potanin, Abramov and others) organized a non-profit organization that would send a machine with reagents from abroad to Russia twice a week, regardless of whether one test tube or the whole machine was ordered, it would already be it would drastically reduce the wait. In addition, it would be great if the capital of such an organization would allow providing temporary loans, i.e. they would carry reagents immediately at the request of the scientist, while he draws up documents for purchase, etc. Although it is absolutely ideal – these are mini-grants with a special status that allows you to quickly deliver a small amount from abroad, but very necessary and urgent reagents, at least to begin with (as an experiment) for those scientists who are currently published in journals with a high impact factor.
If we talk about possible changes on the part of legislation and the state, it is clear that it is probably impossible to solve the problem entirely and immediately. But I would have such suggestions. The passage of the following supplies of reagents from abroad should be carried out with the minimum possible customs clearance (by time and procedure):
1) The status "Addressed to an accredited agent". To accredit organizations or specific scientists to whom there is a certain confidence, for example, scientists who have articles in journals with a high impact factor or have been granted a grant for the purchase of reagents in a facilitated mode (to exclude unscrupulous behavior of persons who do not value their "scientific reputation").
2) The status of "Procurement under an accredited mini-grant". Allocate mini-grants (at least 50-100 thousand rubles per year for the laboratory), for which you can urgently purchase abroad and quickly receive only reagents (or complex consumables such as gel filtration columns).
3) The status of "Test packaging". This is the purchase of a reagent in the minimum possible packaging for test experiments from a limited number of global manufacturers who distribute products only for scientific purposes. If there are fears, for example, of large-scale embezzlement by unscrupulous persons or the import of a large amount of any related products, in extreme cases, it is possible to limit the import of each reagent to one gram or the import of 10 reagents of 10 milligrams (!) each once every two weeks, which will greatly facilitate the situation.
I will repeat once again that there are a huge number of good ideas in this area that still lie on the surface and, by implementing them, Russia can become one of the world leaders. But to do this, you first need to solve the problem with reagents.
– We wish you good luck in the struggle to optimize the delivery of reagents and in further research!
- thanks. In conclusion, if possible, I would like to address Stanislav Govorukhin through your publication.
– Unexpectedly!
– The fact is that I recently watched his film "Not by bread alone." In it, he tells about a certain teacher who invented something revolutionary and then tried to put his ideas into practice, despite any problems and difficulties. It seemed to me that Stanislav Sergeyevich is not indifferent to the fate of scientists, and since he has a certain weight – after all, he is both a deputy and a confidant of the president – maybe he could help us inform "upstairs" about the problem with reagents. After all, there must be Rostislav Petrovich (Alexander Rosenbaum's hero in the film) in real life! And I would like to conclude this interview with a quote from Bertold Brecht's play "The Life of Galileo": "Even a wool merchant should think not only about buying cheaper or selling more expensive himself, but also about how the wool trade could be conducted unhindered at all."
Portal "Eternal youth" http://vechnayamolodost.ru19.08.2014