What is the biotechnological boom of pharmacy?
Valery Yudin, Weekly "Pharmacy", 24.11.2008
Increasingly, achievements in the field of biology at the beginning of the XXI century are compared with achievements in the field of physics of the twentieth century. Albert Einstein and Ernest Rutherford were pushed on their pedestal by a cohort of biologists. It is likely that someone from this cohort is already ready to take their place. Biology, biotechnology and genetics have become a real trend in the world of science. You can read about achievements in these areas not only in specialized publications: today, on the covers of such popular publications as The Economist, Newsweek or People, we are more likely to see a photo of another genius from genetics or biotechnology than, for example, Prince Charles. Well, or, at least, let's read a title like “Biology Reborn. This summer genetic scientist made a breakthrough that will change our future!” (Biology, born again. This summer, a geneticist made a major discovery that will change our future)... Now, perhaps, it is scientists in the field of genetics and biotechnology who will become the real "messiahs" of the future. Perhaps it is they who will be able to someday (perhaps very soon) lift the veil of human existence, predict or even stop diseases that were previously considered incurable.
Genetic data is a very special entity from the point of view of privacy protection. They allow you to identify an individual and may contain confidential personal information. There are many variations of genetic sequences, and this genetic data is similar to fingerprints. They also conceal a significant amount of information about genetic diseases and hereditary predisposition.
Errors in the genetic code are responsible, according to some estimates, for 3-4 thousand hereditary diseases, including Hutchinson's disease, bladder fibrosis, neurofibromatosis, Duchenne muscular dystrophy and many others. Moreover, it is now known that changes in genes play a role in the occurrence of cancer, heart disease, diabetes and many other common diseases. Changes in genes can increase the risk of these severe and widespread ailments. And the disease itself is the result of both genetic predisposition and environmental factors, including nutrition and lifestyle.
Even more disturbing reflections than genetic predisposition to diseases caused the assertion that genes influence human behavior (Hood L., Rowen L., 1997). It has been found that genes influence gambling and a tendency to aggressive (and even illegal) behavior. A study of twins living together and apart showed that "their behavior was largely determined by heredity" (McGuffin P., Riley B., Plomin R., 2001).
Most scientists believe that people's behavior and diseases are mainly determined not by single mutations or genes – rather, most aspects of human development "represent the culmination of a lifelong interaction between the genome and the environment" (Peltonen L., McKusick V.A., 2001). Thus, the scientific data available today clearly do not indicate that a person's genes cardinally affect the further development of his disease or character traits. Such conclusions often turn out to be only hypotheses or even speculation.
Nevertheless, genetics is an area of scientific development in which rapid changes are taking place. The amount of knowledge about the human genome is rapidly increasing. The human genome sequence was first published in February 2001. This immediately sparked debate about the future of genetic technology and its impact on society, including privacy. U.S. Senators James M. Jeffords and Tom Daschle made the following comment: "One of the most difficult tasks of our time is to determine the proper balance between the protection of privacy and the honest use of genetic information" (James M. Jeffords and Tom Daschle, 2001).
Pharmacy is not left out of this biotechnological and genetic boom. Increasingly, we read in the news that pharmaceutical giants are buying up biotech companies in bundles, as during seasonal sales, or those who do not have enough money, at least agree on cooperation and joint development of biotechnological drugs. As you know, there is no smoke without fire. And the biotechnological "smoke" has its own "fire", which fuels the interest of pharmaceutical companies: with the help of discoveries that have occurred in recent years, it has become possible to create drugs, and with predictable properties and side reactions. The development of biotechnology also makes it possible to conduct post-marketing studies, also called phase IV clinical trials, when it is necessary to study the effectiveness and adverse reactions of the drug on a wide sample of patients, sometimes reaching several hundred thousand participants.
Previously, the system for assessing adverse reactions was based on their statistical assessment and mathematical determination of the number of risks within the sample. The role of biology was often neglected. This was partly justified by the fact that large material and human, as well as time resources were required to assess biological mechanisms or genetic predisposition to the occurrence of adverse reactions: it was necessary to identify existing biomarkers in laboratory conditions, obtain copies using sufficiently time-consuming and not painless procedures for patients, test clinical samples, statistically analyze the results. Pharmacogenomics is a subspecies of biotechnology that studies the genome of a person or another biological object in order to find the most suitable medicine for a specific genotype with maximum effectiveness and minimum side effects. Pharmacogenomics, without involving patients directly, but only using their DNA base, allows postmarketing studies to be carried out quickly and cheaply enough, using different genetic material of individuals of different races and ethnicity.
In the countries of Western Europe and the USA, the possibility of using huge databases in the field of insurance to identify rare cases of adverse reactions and register them is widely discussed (Zavras A.I., 2004; Walker A.M., 2001). Actually, even obtaining DNA in order to form a base for such studies is no longer a painful procedure - for this it is quite possible to use the method of collecting epithelial cells (Harty L.C. et al., 2000). Small amounts of DNA can be increased using the whole-genome DNA amplification (WGA) method (Hosono S. et al., 2003), and the high performance of the genotyping platform allows simultaneous testing of hundreds of thousands of polymorphic genes (Cox D., 2003). This also contributes to the development of new statistical methods that take into account the features of the haplotype (a combination of alleles on one chromosome), as well as advanced data retrieval methods that access maps of the human genome and make it possible to determine genetic differences in the sequence and identify "risky" genes. We are not talking about persistent conversations about creating an individual drug for everyone – taking into account all the features, indications and contraindications.
As we can see, biotechnologists, following geneticists, have swung wide – and we are about to go back to eugenics, the science of human improvement.
Where is the dog buried?One of the most important discoveries of recent times is that it has finally been established that every person has a set of nucleotide sequences that causes a particular genetic disease, which occurs only when the number of these sequences exceeds a certain threshold concentration.
Eric Lander, director and founder of the Broad Institute research group, collaborating with Harvard University and the Massachusetts Institute of Technology, said about how understanding this mechanism will contribute to the development of treatment methods: "There are many reasons that affect the, will a person get sick: this is both a direct predisposition, and the impact of external factors, and a combination of these two reasons."
It is known that some diseases are becoming more common nowadays, for example asthma. However, this is not because genes have somehow changed, but due to changes in environmental factors. Therefore, when we say that there are some genetic risk factors, we must remember that genetics explains only a certain part of the mechanism of the disease, and not its entire mechanism from beginning to end. But with most diseases, we don't even have an idea what kind of genetic failure underlies these diseases. We don't know where or what went wrong.
Genetics, of course, is an excellent way to explain a malfunction in the system; this science can help us figure out exactly which genes and biological mechanisms underlie a particular disease. But this does not mean that, having understood this mechanism, you will be able to find a cure for its treatment. It is likely that the best treatment in this case will not be medicine, but a regular diet, believes E. Lander.
Geneticists have developed a technology that allows you to focus on studying smaller DNA particles of the entire genome, and not just some specific genes. But how do you know exactly where to look for the place where the crash occurred? We can't know that for sure. Despite the fact that we live in an era of great discoveries in the field of genetics, we do not have specific goals for studying.
However, it is unthinkable to study the entire genome at once! Therefore, having decided, for example, to work on the study of the problem of the occurrence of cancer, we can say that the chromosomal mutation that led to the occurrence of cancer can occur anywhere. If you study such a hereditary disease as diabetes mellitus, then the inherited cause of it can also be everywhere. In other words, at the beginning of the search, in any case, some assumptions are put forward, hypotheses that the cause of a particular disease is located on a particular DNA site. Of course, we have no choice but to study this area, which is equivalent to fortune–telling on coffee grounds or tossing a coin - you will get it or not.
In the twentieth century, we did not know the biological basis of most diseases. In our biotechnological age, the study of the genome has allowed us to gain knowledge in the field of biological causes of various pathologies. But this does not mean that we can now cure all diseases. And yet, for the first time, we have come close to understanding the true mechanisms of the development of certain diseases.
Speaking about the future prospects, Dr. E. Lander believes that in the next 5 years we will enter a period when biotechnologies will be used in clinical research.
Per aspera ad astra, or from mushrooms to NeanderthalSince genomes have already been sequenced (that is, decoded) for both humans and other organisms, there is interest in how genes interact and work at the level of the system, the whole organism.
This is what David Botstein, professor of genomics at Princeton University, is currently working on.
Most of the career of this scientist was devoted to the study of yeast, which turned out to be a good material for genetic, biochemical and evolutionary research. Currently, he is trying to figure out how genetic chains interact with each other, since for the first time scientists have approached the possibility of seeing the overall picture of the simultaneous work of genes.
Why yeast mushrooms? And how can they help in the cure of diseases? The thing is that by suspending the growth and development of yeast fungi in certain conditions inside their cells, it is possible to achieve the suspension of metabolic processes in which substances such as glucose remain unspent. In another case, their growth will be interrupted randomly, and glucose will be wasted. This is also a feature of the growth of cancer cells. They cannot stop the cell cycle in the usual way, and glucose is wasted.
D. Botstein's work is based on the idea that, having understood the integration of metabolism and the cell cycle of yeast fungi, we can understand how such processes take place in more highly developed organisms, such as, for example, human. After all, the basic organization of vital functions of both simple organisms (fungi) and more complex ones (birds or humans) is largely similar.
D. Botstein believes that there is hope that scientists will be able to identify something that will contribute to the production of protein, which in turn will inhibit certain mechanisms of disease development. Despite the fact that man has gone very far ahead in his development compared to other organisms, and even more so yeast, and it will be very difficult to find any direct relationships in the mechanisms, nevertheless, work on this problem will shed light on how the system works, and then identify similar systems characteristic of for more advanced organisms, and work on them already.
Another scientist, Svante Paabo, director of the Department of Evolutionary Genetics at the Max Planck Institute in Leipzig, Germany, is known for his research on mitochondrial DNA isolated from fossilized Neanderthal bones. This scientist participates in the implementation of an even more extraordinary project of the company "454 Life Sciences", owned by the company "Roche" (you can find out more about the project on the official website of the company). In it, a group of scientists, led by project vice president Michael Egholm and its founder Jonathan Rothberg, are trying to sequence the Neanderthal genome. The main difficulty of the task facing the researchers is the poor quality of the genetic material that was extracted from the bones that had lain in the cave for 38,000 years. Therefore, one of the main tasks is to process a huge number of nucleotides.
Along with this, the genome of chimpanzees was also sequenced. It turned out that the difference between us and chimpanzees is 35 million pairs of nucleotides. Scientists of the 454 Life Sciences project proceed from the fact that chimpanzees and we diverged in evolutionary development 5 million years ago, and Neanderthals and we – only 500 thousand years ago.
The idea of the scientists of this project is to analyze the available 35 million pairs of nucleotides in humans, Neanderthals and chimpanzees, and then compare to whom the Neanderthal genome is closer. In the several million pairs that have already been deciphered, the DNA of a Neanderthal only matches the DNA of a chimpanzee in 4% of cases; otherwise it is closer to homo sapiens. And scientists are interested in just these 4%, in which they hope to find genes responsible for higher behavioral functions.
If researchers manage to find out what the genetic differences between homo sapiens and its closest relative, homo neanderthalensis, are, scientists will get an answer to the question: how modern man was able to spread across the planet, how he managed to develop to such a high level, which allowed him to develop high technology, art, etc. Eventually, after studying and understanding the genome sequence, scientists will be able to create a catalog of all the genetic changes that occurred on the way of the formation of the Neanderthal into modern man. In turn, this will help determine which genetic differences are unique to modern humans.
Ultimately, everything that these scientists are doing may become medically important. It is likely that they will be able to unravel, for example, why a person talks and how this ability has developed. And this will allow us to solve problems related to speech more effectively. This may also be true for a disease such as autism, and many others that concern each individual.
To be continued…
Portal "Eternal youth" www.vechnayamolodost.ru25.11.2008