Genetic miscellany (from the definition of life to the influence of happiness on genetics)

{ "translated_text": "It Is Hard to Be a God\nAttempts at artificial creation of life have a long history. When Paracelsus speculated about obtaining mice from dirty shirts and sprouting wheat, life seemed something simple, and its emergence a routine matter. As the unimaginable complexity of living systems became understood, hope for their manufacture almost vanished, but it was revived by the successes of molecular biology in recent decades.\nOne of the attempts to construct life is currently undertaken at Los Alamos, the American scientific center famed for the atomic project. The life‑building effort is led by Danish physicist Steen Rasmussen, while the chemical side of the project is headed by Chinese scientist Liaohai Chen. In addition to this team, dozens of other research groups conduct similar experiments. So why did the presentation on the initiated project open with the slide “We are not crazy”? It turns out that Rasmussen intends to create life of a chemical nature different from terrestrial life. The scientist does not go beyond organic chemistry, but seeks molecular solutions that would allow the structure of living (or pseudo‑living) systems to be simplified to the utmost.\nTo appreciate the immense difficulty of the task, one must first clarify what life is. As is well known, there is no universally accepted definition¹, but several approaches to formulating one exist. Since Earth organisms are based on proteins and nucleic acids, one can, following Engels, characterize life by its biochemical basis. Alternatively, life can be described by enumerating characteristic properties of known living beings. The most general approach is the one that does not tie the phenomenon of life to specific classes of substances or particular phenomena, but treats it as a thermodynamic phenomenon. Life is an evolutionarily improving reproduction of a characteristic structure powered by an external energy source according to an internal program. When discussing terrestrial life, we can detail the characteristic structure (a cell with a lipid bilayer membrane, a program in nucleic acids, energy conversion with a key role of proteins, etc.) and typical manifestations of its functioning.\nIs it necessary, when formulating the concept of “life”, to emphasize evolutionary development? Probably yes, because this is what distinguishes “real” life from any arbitrarily perfect mechanism. All features of living systems are the result of evolution. This means not only that each feature has been refined by selection over vast time, but also that however complex modern life is, all its characteristics could have arisen only evolutionarily—by improvement of initially relatively simple adaptations. In Earth’s evolution Athena could not have sprung from Zeus’s head—it had to undergo a 4 billion‑year developmental path, retaining traces of that path in its structure.\nAccording to the given definition, neither viruses nor simpler molecular‑genetic systems should be considered alive. A virus is a nucleic‑acid molecule containing the program for its assembly, protein molecules that deliver this acid, and sometimes a few other “details” taken from the host cell. All work of producing the virus is performed by the cell—the actual carrier of life. If we deem a virus alive, we must also consider a “letter of happiness”, containing instructions for its own rewriting and propagation, as alive.\nViruses have already been synthesized artificially: the mouse poliomyelitis virus was assembled monomer by monomer. Although the artificial virus was identical in properties to the natural one, this result is not yet regarded as the creation of life.\nTechnologies tested on viruses are now being attempted on cells. In Maryland, a team led by Craig Venter, one of the pioneers of the human genome decoding who provided not only his own genome but also refined sequencing methods for this task, is trying to recreate, molecule by molecule, one of the simplest cells—Mycoplasma genitalium, the agent of a human sexually transmitted infection. Mycoplasma operates with only 517 genes, and their number can be further reduced (Venter is already ready to discard more than half of them). By disabling functional blocks in Mycoplasma one by one, the scientist plans to describe the simplest self‑reproducing construct and then assemble it from individual molecules.\nRasmussen is attempting to create a minimalist alternative based on other compounds. For example, he has decided to abandon the most characteristic feature of known life: membranes. Biological membranes, based on lipid bilayers, seem an inseparable characteristic of life. They delimit the internal environment of the cell and partition complex cells into separate compartments. Rasmussen, however, intends to synthesize protocells—so‑called micelles (nanoparticles existing in aqueous media) assembled by hydrophobic and other molecular interactions. The core of micelles, like that of membranes, will consist of lipids—fat‑like substances to which other molecules will bind. Micelle sizes are 5–10 nm (a tiny clump even compared with the extremely small Mycoplasma genitalium cell, which reaches 200–250 nm).\nRasmussen is dissatisfied with the properties of both DNA and RNA—the information carriers of terrestrial life. Hope is placed on peptide nucleic acid (PNA)—the creation of Danish scientist Peter Nielsen, one of the participants in the described project. PNA combines matrix‑copying ability with enzymatic activity. Although this substance is not found in living nature today, Nielsen hypothesizes that PNA could have been the biopolymer from which “large” life once evolved.\nSince PNA is electrically conductive, attaching a photosensitive molecule to one end could enable movement of a photon‑excited electron along the peptide nucleic acid chain. Ultimately, the electron should trigger restructuring of a “food” molecule added to the culture medium. As a result, “food” molecules should yield protocell components, and molecular interactions should attach new molecules to the micelle, promoting its growth. When the micelle grows, it will lose stability and split into two parts. By adding “food” to the medium, removing waste, and supplying light energy, a reproducing population of artificial protocells would be obtained. The alternative life that Rasmussen aims to create will not be able to exist autonomously under Earth conditions, but biotechnological applications for it are already being explored.\nCan this phenomenon be called life? The project’s author says yes, confident that even a single “life” cycle of the new construct would constitute a scientific victory. However, not everyone agrees. One of the fundamental properties of life is the potentially unlimited temporal preservation of its properties—immortality. A complex organism cannot be immortal, but a self‑reproducing population can. Potential immortality of life is tightly linked to its capacity for evolution. New life can be said to have been created only when, under culture conditions, selection of alternative protocell designs begins, leading to improvement of their metabolism and reproduction. If evolution was a condition for the emergence of “large” life, the independence of “small” life can be judged only after its first evolutionary steps.\nWell, let’s see what Rasmussen manages to achieve.\n\n1 This situation is paradoxical for the exact sciences but typical for biology. Unambiguous definitions are lacking not only for life but also for species, organism, population, adaptation, evolution, biosphere, and many other key biological concepts. Back to text\n\nGenetic Express\nWhat good is it that science has identified genetic predispositions to many diseases? How can this help an individual patient? The classic method is for a genetic specialist to interview the patient, learning what illnesses affected his relatives. The interview may lead, for example, to the conclusion: “since many of your relatives are hypertensive, you may have a genetic predisposition to this disease; you should lead a healthy lifestyle before the first symptoms of high blood pressure appear.” If this truth is communicated to a person already ill, nothing changes: nothing can be done, it is written in the genes. But if a healthy person hears such a verdict, might he adopt a healthy lifestyle and, “like a fool with a clean neck,” die without ever knowing he had no predisposition to hypertension? One could argue that he did not lose, because he lived healthily. Then why cloak the promotion of the latter in the mantle of genetic counseling?\nCertainly, there are a number of serious anomalies whose transmission across generations can be traced by classical methods. Fortunately, these anomalies are rare. For the majority of citizens predisposed to vascular, metabolic, or other disorders manifesting in adulthood, classic counseling methods amount to coffee‑ground divination. Until accurate, fast, and cheap methods for analyzing an individual’s disease predisposition appear, the benefit of genetic approaches in combating the most common diseases will be modest.\nIt is possible that the situation will be remedied by a technology developed at the University of Queensland, Australia, using geneballs (“gene‑balls”). In fact, this is a modification of bio‑chip technology: microscopic pores on the surface of a tiny quartz sphere (a fraction of a millimeter) contain DNA samples complementary to sequences of particular defective genes. “Gene‑balls” are placed in biological material containing the DNA of the person under investigation (e.g., a drop of blood with white‑cell DNA). If the material contains DNA sequences complementary to the test ones, they bind to the surface of the “gene‑ball”. During hereditary analysis, the researcher assembles the required set of “gene‑balls” for the patient and processes it with the biological material. Then the “gene‑balls” are illuminated by a laser, which determines which of them contain bound DNA.\nThe described technology is relatively inexpensive (the diagnostic complex costs $30 000, and analysis of a single patient can be quite cheap). Although there is no scientific “breakthrough” in the new idea, it is well suited for wide use. Has a diagnostic revolution occurred?\nNot quite. Mechanisms of genetic predisposition are known for far from all diseases. On the other hand, the “gene‑ball” technology may be useful for searching genetic markers in mass screenings of patients and healthy people. Incidentally, it could also be used to search for other markers—for example, to determine from a drop of blood whether a person is suitable for high‑performance sport. And interestingly, are there genetic markers correlating with a person’s willingness to confront management?\n\nShall We Train on Dogs?\nAustralia has decided to introduce genetic passports for pure‑bred dogs. The new procedure will initially be voluntary, and from 2008 will become mandatory—only animals possessing a genetic passport will be allowed to breed.\nOf course, Australians did not take this step without reason. The issue is that dog breeds are small groups with reduced genetic diversity, in which close‑inbreeding is widely practiced. If a breed founder introduced a defective gene, close‑inbreeding can sharply increase the “concentration” of that gene, shortening the lifespan of many breeds (especially old and rare ones) and eventually leading to the extinction of historically valuable breeds.\n[IMG_1]\nMost defective genes manifest only in the homozygous state (in individuals with two identical copies of the dangerous gene) and are hidden in heterozygotes (carrying one defective and one normal version). Classical methods can identify a heterozygous disease carrier only by analyzing its offspring (and producing defective puppies in the process). Modern methods allow detection of carriers of dangerous breed genes from a swab of skin epithelium containing live cells, and their removal from breeding. To avoid confusing rams with goats, tattoos and sub‑cutaneous microchips will be used.\nIn the past, technologies developed for humans (individual passports, pedigree accounting) were transferred to cynology. Methods of “breed improvement” proposed by eugenics are now fully employed in dog breeding. The new approach enables complete control over the spread of undesirable genes and their removal in a single generation. Conversely, practical experience with genetic diagnostics, individual identification, and use of the data for eugenics (i.e., selection) may later be useful for transferring “progressive technologies” to humans.\nAfter all, dogs were the first to fly into space…\n\nIs Happiness in Money?\nThe fact that perception of quality of life influences health is not news. Each of us can observe this in our surroundings. It is, of course, difficult to distinguish primary from secondary effects and to determine whether a person’s health deteriorates because his life fell apart and he fell into depression, or whether ruined health caused problems in the emotional sphere and social interactions. Clearly, these two problem complexes go hand in hand.\nMoreover, an absolute assessment of quality of life does not exist and cannot exist. Compare the life of a feudal aristocrat a few centuries ago with the existence of a modern clerk. In terms of domestic comforts, hygiene, dietetics, health care, safety, tourism opportunities, and ways of mental relaxation, life has advanced far ahead. The only difference is that the feudal lord might not have expected anything better from life, whereas the clerk looks at “stars” and nouveau‑riches, envies them and feels deprived.\nFormulated observations may seem banal. What are their psychophysiological mechanisms? To explain one of the “fresh” scientific results, one must recall that most body cells contain a “clock” limiting the possible number of their divisions. Chromosome ends have special regions—telomeres. With each cell division a small piece is “cut off” from them. After telomeres shorten to a certain level, cells lose the ability to divide. Only germ‑line cells, as well as some stem and tumor cells, are exempt from this effect.\nOne potential anti‑aging approach is linked to this phenomenon. If we could halt or reverse telomere shortening—the “leather” of the cell—we would remove a major constraint on lifespan. Enzymes capable of this are known; the task is to ensure they work as desired. However, that is not the current topic.\nA British‑American group led by Tim D. Spector found that the rate of telomere shortening depends on socioeconomic status! Studying chromosomes of volunteers, researchers discovered that, for example, among women of passport age the telomere length difference between social “cremes” and “lumens” corresponded to seven years. Naturally, the life reserve shrank faster in low‑status groups. The same phenomenon was confirmed by twin studies of genetically identical people living under different conditions.\n\nGreen Informants\nThe task of forensic science is the reconstruction of past events, and any data—even the most unexpected—can help.\nInternational human‑rights organizations, with staff from the University of Birmingham, continue to search for mass graves of terror victims in Bosnia from 1992–95. About four thousand people are still listed as missing. Many communal graves have already been found. They are studied to determine the “handwriting” of the executioners. It turned out that such graves are covered by specific vegetation, in particular nettles. Each plant species has a unique set of pigments and spectral characteristics, which are influenced by growth conditions. Thus, analysis of these vegetation parameters from satellite imagery allows locating burial sites.\nAustralian experts are already ready to use seeds and other plant parts attached to shoes and clothing for crime reconstruction. The idea itself is not new: if a suspect’s clothing is covered in mud, one can safely say he has been on a weed‑infested field. The technological novelty lies in decoding DNA sequences of the plant fragments, enabling identification of the population they belong to and reconstruction of the subject’s route.\nThus, escaping the close scrutiny of green informants is becoming increasingly difficult.\n\nD. Shabanov. It Is Hard to Be a God // Kompyutera, M., 2005. – No. 6 (578). – pp. 18–19\nD. Shabanov. Genetic Express // Kompyutera, M., 2004. – No. 39 (563). – pp. 13–14\nD. Shabanov. Shall We Train on Dogs? // Kompyutera, M., 2004. – No. 38 (562). – p. 17\nD. Shabanov. Is Happiness in Money? // Kompyutera, M., 2006. – No. 29 (649)\nD. Shabanov. Green Informants // Kompyutera, M., 2005. – No. 31 (603)" }