13 March 2009

Why do we need investments in fundamental science

Estimate without foundation
Why is it necessary to finance fundamental scienceVictoria Doronina

Ph.D., Institute of Cellular and Molecular Biology, University of Newcastle upon Tyne, UK

Published on <url>Fundamental science was hit even before the crisis.

In the governments of many countries that can afford such luxury, the idea has appeared that science is only worth something when its findings can be put into production here and now. This is understandable for the now independent countries – the former republics of the Soviet Union, where there is often no money to finance healthcare and education. But, for example, in rich Britain, this approach began to develop, although for other reasons: it was decided here that one of the foundations of the "knowledge economy", based not on production, but on the sale of know-how, would be the rapid turnover of knowledge.

However, it is not clear how quickly knowledge is ready to "turn around". We will consider this question on a concrete example of the introduction of one of the achievements of fundamental science into life.

As we know from the school curriculum, the protein is synthesized on matrix RNA (mRNA), starting with three starting nucleotides (codon) of AUG, which encode the amino acid methionine. The transport RNA (tRNA) associated with methionine recognizes the AUG codon and takes its place. All subsequent amino acids are delivered by other transport RNAs that recognize the corresponding codons. All this process is controlled by the ribosome – a complex complex consisting of special ribosomal RNAs and proteins. The ribosome catalyzes the formation of a chemical bond between the previous amino acid and the subsequent one, as a result of which a chain of amino acids – a protein - is gradually formed. At the end of the mRNA encoding the protein, there is one of the three codons that no tRNA corresponds to, the so-called "stop codon". When the ribosome reaches it, special ribosomal proteins – termination factors – release the synthesized chain of amino acids. If a mutation in a gene has led to the appearance of a stop codon in its middle, only part of the protein will be read from the mRNA, it will be short and defective.

Back in the late 1950s, shortly after deciphering the structure of DNA, Watson and Crick suggested that the genetic code is universal. That is, knowledge of the principles of the organization of genetic information in non-nuclear organisms (bacteria) will be applicable to more highly organized, nuclear organisms, which include humans. The first mutations that led to the stop codon being in the middle of the gene were obtained in the early 1960s in E. coli viruses, bacteriophages T4, by two groups of researchers - led by Edgar in the USA and Kellneberg in Switzerland. Viruses do not have their own protein-synthesizing apparatus, only the instructions for synthesis are DNA. Bacteriophages use ribosomes and all the factors necessary for the synthesis of bacteria, introducing their DNA into the host cell. Therefore, by studying the genetic organization of a virus that contains much fewer genes than the simplest bacterium, it is easier to draw conclusions about how the reading of information in a bacterial cell is organized.

In the late 1970s, research began to develop on more complex objects. Baker's yeast was chosen as the simplest model: like humans, they belong to nuclear organisms (eukaryotes), many fundamental processes, such as protein synthesis, in yeast follow the same principles as in humans, for example, their ribosomes are of the same size (bacterial ones are smaller, because ribosomal RNA and ribosome proteins are arranged somewhat differently in them). At the same time, technically working with yeast is not much different from working with E. coli. They grow in a simple liquid medium and on Petri dishes, mutations are easily obtained using chemicals and ultraviolet light. In the Soviet Union, these studies were conducted in Moscow, in particular, at the Institute. Engelhardt, in the laboratory of the late L. L. Kiselyov, who was a world-class authority in the field of studying the processes of protein synthesis.

As a result of the work, including by Soviet scientists, yeast mutations of the same type as those of bacteriophages and bacteria were obtained. By that time, it was already known that some antibiotics affect protein synthesis in bacteria. For example, the well-known streptomycin causes errors in the work of the ribosome in E. coli. When studying yeast, it turned out that some substances also change the work of ribosomes in such a way that ordinary tRNAs recognize stop codons and an almost normal protein is read from an "abnormal" mRNA.

In the 1980s, research began on the molecular mechanisms of hereditary human diseases. It turned out that some of them are caused by the same type of mutations – stop codons in various genes, which leads to the absence of a certain normal protein. This is caused, for example, by cystic fibrosis, which is expressed in disorders in the respiratory and digestive systems, and another disease – progressive muscular dystrophy. It is still impossible to eliminate the cause of the disease by modern methods, because it requires "rewriting the instructions", that is, DNA. In the 1990s, scientists suggested using antibiotics to alleviate the symptoms of such diseases, which, as was first shown in yeast, increase the percentage of reading stop codons by random tRNAs.

It is impossible to correct the instruction itself, which leads to the appearance of a defective protein, in this way, but it is possible to increase the number of errors of the usually accurate ribosome, which will lead to the reading of a protein of normal length. But, firstly, for the noticeable effect of existing antibiotics, for example, paromomycin, large doses of drugs are needed that cause serious side effects. And secondly, the result of the action of antibiotics depends on the specific mutation, which differ from person to person.

In the late 1990s, one of the scientists working in the field of studying the mechanisms of protein synthesis in yeast, the American Alan Jacobson, decided to use them to find substances that specifically increase the reading of stop codons. His group began the search with a large number of low-molecular substances that were added to yeast. For several years, two or three candidate substances were selected from several tens of thousands, with which clinical trials were conducted. First on mice, now on humans (2007), patients with cystic fibrosis. In most people, when taking the medicine, relief of the symptoms of the disease was obtained without serious side effects. There is a high probability that the most promising of the "candidates" will be introduced into the clinic.

And now let's look at the time frame. More than 50 years have passed from the first research to a specific product. Currently, Alan Jacobson would have received money to develop a system for testing substances on yeast. But with money for the previous stages (the study of yeast mutants cut off from life, and even more so bacteriophages, which are difficult to link to a specific disease) it would be bad.

Politicians rarely think within longer terms of the next election: 3-5 years. Taking into account the crisis, this decision-making horizon narrows down to the annual budget. And those who promise to develop and implement a miracle technology today receive funding. But such technology is not created from scratch. It requires a material and technical base and the qualifications of specialists. And if the first is solved by allocating sufficient funds for the purchase of equipment, the second is the same long–term project that is being laid decades before today. This can be seen in the example of South Korea, where good funding in the absence of a Western tradition of training has not yet led to world-class results.

Perhaps the understanding that science, like art, is divided into one that can be applied in the foreseeable future (the equivalent of mass art) and one whose results are not visible in the next 10 years (elite) would lead to a reassessment of the importance of fundamental science. And just as when allocating budget money for culture, politicians do not consider funding pop groups, but allocate money for museums and libraries, they also need to understand that applied science can take care of itself to a greater extent than fundamental science.

In Britain, fundamental science, with rare exceptions, is university science. Teachers are selected based on their scientific achievements. Their salaries are paid for the academic load, and they receive money to finance their own laboratory from external grants. In the conditions of the financial crisis, researchers lose their jobs, but the basis, the teachers themselves with their unfashionable interest in fundamental science, remain. This is a half-measure, but it somehow works.

Perhaps the problems of training specialists with sufficient horizons, and conducting research that is not designed for a quick result, can be solved in the post-Soviet space by allocating money on a competitive basis for university science. In the meantime, in Russia, the lion's share of the budget allocated to science goes to the Academy of Sciences, and the lion's share of the remaining gets one center – MSU.

No one is trying to build a house on bare ground, without a foundation. The allocation of money for applied, but not fundamental science can be compared just with the allocation of money for the construction of walls with a dash in the column "foundation".

Portal "Eternal youth" www.vechnayamolodost.ru13.03.2009

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