Angelo Serra
Professor Emeritus of Human Genetics. Università Cattolica del Sacro Cuore, Rome. Member of the Pontifical Academy for Life I. The genetic revolution: the gene
1. The discovery of G. Mendel and the subsequent search for the gene . The year 1900 marked the beginning of a revolution in biology, which was a growing in size and aggression throughout the twentieth century. That year, H. de Vries, K. Correns and E. Tschermak had managed to find in the course of study activities conducted independently of one another, work in 1865 when Gregor Mendel (1822-1884) reported the results eight years of laborious, but brilliant, research (1856-1863) and brought to the attention of the scientific community that the contribution had been ignored until then. By studying the hybridization of plants, he had discovered the "laws of inheritance", ie the transmission from generation to generation of phenotypic traits - such as, for example, flower color and shape of the half - and had formulated the hypothesis concluding that: a) those characters had to be associated with "separate unit particle" that is different for each character, and b) these "units" were to be present in the gametes, and they carried and transmitted intact from generation to generation.
particle was necessary to discover these units and how they were transmitted from parents to children. The steps are succeeded with remarkable speed. Cell studies had already revealed that during the steps leading to its propagation, it is formed of particles in particular called "chromosomes." In 1902 a young American student, WAS Sutton (1877-1916), described his observations on the behavior of the 22 chromosomes of an insect, the Brachistola magna during the proliferation of somatic cells (mitosis) and during the formation of gametes (meiosis) and traced the mode characteristics. The following year, 1903, became aware of the work of Mendel, published a critical work entitled The heredity chromosomes (see WAS Sutton, The Chromosomes in Heredity , "Biological Bulletin, 4 (1903) pp. 231-251). By combining into a single interpretation of facts and ideas of their own area of \u200b\u200bresearch cytology with those of the genetic research of Mendel, Sutton explained his hypothesis that we finally opened the way for the experimental verification of one of Mendel as "separate units particulate "Mendel had found in the chromosomes, and indeed each of these was to bring more than one of these" unit-character ". It followed that these had to be "inherited together and, in anticipation of future discoveries, concluded:" It is conceivable that the chromosomes can be divided into smaller entities [...] which may be dominant or recessive regardless. " It was precisely these 'units' postulated by Mendel, and W. them Johansen (1857-1927) in 1909 was called the "genes". In 1910, their localization in the chromosomes, suggested by Sutton, TH Morgan was experimentally confirmed by the demonstration of transmission, always linked to the X chromosome, the character "eye color" in Drosophila . Confirmation finally and successfully tested few years later, in 1913, by AH Sturtevant. He, using six phenotypic traits that, in Drosophila , were found to be associated in the X chromosome, showed that they were separated from each other and arranged in ordered series, and the publication of his research concluded with the statement: "These results provide a new argument in favor of the chromosome theory of inheritance, for they strongly suggest that the factors studied are arranged in a linear series, at least mathematically."
In 1913 the gene was, therefore, an entity whose existence on the material was no longer possible to doubt and, above all, was to bring a definite "information". Indeed, other research - including, in particular the trials of "mutations" induced by radiation - opened as claimed HJMuller, "the hope that it could face problems in the new angle of the composition and behavior of genes." Solving these problems took years of hard work which contributed to many researchers and very effective. Only when it was possible to analyze the genetic material at the molecular level was actually and finally understood the real nature of the gene. They spent so many years. During
this time developed a number of other fields of inquiry, which will return: biochemical genetics, cytogenetics, formal genetics, population genetics and medical genetics, all of high importance especially in view of scientific studies and practical applications in both the plant and animal and human, but, again in 1958, RE Goldschmidt insisted: "I have repeatedly stressed that the whole classical genetics can be described in terms of the corpuscular gene, but when we ask what is this gene material, the facts compel us to abandon this simple concept (RE Goldschmidt, Theoretical Genetics, Berkeley 1958, p. 188).
2. The nature of the gene . In broad strokes, the answer to this question took place through four stages of an intense and painstaking research that involved a significant number of Nobel laureates.
The first line of research - which contributed in particular T. Caspersson, OT Avery, A. Boivin, and DA Hershey - led to the demonstration, finally reached between 1940-1952, the nature of the substance that carries the "genetic information" - and therefore an essential part of the constitutive gene - is chemically the deoxyribonucleic acid (DNA).
The second line of research led knowledge of the particular chemical structure of DNA, which would then open the way to the analysis of gene E. Chargaf the statement is, in its main part, of four nitrogenous components: adenine, guanine, cytosine, thymine (see Chemical specificities of nucleic acids and mechanism of Their Enzymatic degradation , "Experientia" 6 (1950), pp. 201 -209), and, in 1953, JD Watson and FH Crick speculated it the "double-helix structural model," emphasizing that the specific information of each gene had to be attributed to a well defined and limited sequence of four bases that made up its DNA (see Molecular structure of nucleic acids. A structure of deoxyribose nucleic acid , Nature 171 (1953), pp. 737-738 and 964-967).
The third line of research, driven in particular by HG Khorana and M. Niremberg was oriented to the deciphering of the genetic code, that is the language in which this information is written, and as it is the "decoding" (see HG Khorana, polynucleotide synthesis and the genetic code , "The Harvey Lectures, Series 62 (1968), pp. 79-105, and M. Niremberg, RNA codewords and protein synthesis. The effect of trinucleotids upon the binding of ribosomes to Srna, Science 145 (1964) pp. 1399-1407). It was from surveys conducted during the decade of the sixties - basically geared to the analysis of some major stages of the mechanisms of protein synthesis and attempts to synthesize polypeptides in vitro using the synthetic polynucleotides - who emerged as the "functional structure" of gene and its mode of action, and was definitively established the principle that the gene controls the phenotypic potential of cells and organisms dictating, at least in large part, the structure of proteins.
The fourth line of research, the "artificial synthesis" of individual genes and analysis of their activity, was to be the rebuttal of what had been hitherto demonstrated. In 1976, the group of HG Khorana and his twelve associates who had synthesized the gene for alanine tRNA in 1970, but still not working, and RW Holley and his seven co-workers, who had shown what was missing for the operation, was synthesized tyrosine tRNA gene, consisting of a chain of 36 nucleotides preceded by an initial portion of "non-transcribed" of 126 nucleotides and followed by a last short piece, it also "is not transcribed. The gene, artificially produced, embedded in a bacteriophage for the same mutant gene, had worked perfectly correcting the error that it prevented proliferation. It was the irrefutable rebuttal of the structure and function of the gene (see Th.H. Maugh, The artificial gene. It's synthesized in cells and it works, "Science 194 (1976), p. 44).
The "secret of life" was finally found! The set of genes or "genome", present in every living organism, must be recognized as the "floor-plan" that each carries in himself inscribed, and whose activities, coordinated and integrated with thousands of other information, depending its development and its operation. At the "genomic revolution" had the task to proceed, through genetic engineering, a more amazing knowledge, who opened the century of biotechnology.
II. The "genetic information"
1. The organization of information . What is written in the genes can be correctly determined analogous to a "word" that "meaning", a port that is "information". When the passing of a magnetic tape on which are recorded the words, listen to voices such as 'pear', 'pear', 'however', each of these would you propose to mind an "information" different. So is every gene: each brings a specific message, rightly said "genetic information". And, since a simple observation shows that every living being has a greater or lesser number of genes, it is logically necessary to their "organization" both structural and functional, which are drawn here are a few items.
a) The genetic information is "written" in the macromolecules of DNA of varying length, consisting of two paired strands, coiled upon one another, each of which succeed in different order depending on the genes, molecules adenine (A), guanine (G), thymine (T) and cytosine (C), inserted on a skeleton phospho-desossiribosilico, face regularly so that in a filament the other was connected to a T (AT) and the C of G with one strand of the other (CG), thus forming a series or "sequence" of "base pairs (bp), according to the scheme:
ATCCGTAATGCA ......... ..........
::::::::::::
TAGGCATTACGT ......... ..........
These molecules are not, however, arranged at random. Genetic information is, in fact, written in "code" and the elements of this code, the vast majority of genes are 64 triplets, arising from the combination in groups of three of the four molecules A, C, G, T; triplets which correspond to very specific amino acids, whose sequence depends on the chemical characteristic of the thousands of proteins in the body.
b) The genetic information is collected and "organized" - for the most part-in 'chromosomes', which appear corpiccioli visible under the microscope during the process of cell multiplication superspiralizzazione and derived from long strands of chromatin constituents present in the cell nucleus during the resting phase. In them are "housed" in the genes data loci, spaced from one another by considerable intervals, often occupied by DNA - in what is now known - non-coding. In the human species - to be held here mainly because - in the normal chromosomes have 46, and two by two "counterparts", ie with the same set of genes; of them, one comes from the father and the other from the mother. May be similar to bringing a total of 46 volumes of about 7 billion pairs AT and CG: quantity 3500 would take volumes of 1000 pages each with 2000 base pairs per page. A small amount of genetic information is contained in the "mitochondria" in a double-stranded circular DNA, in humans, is 16,569 base pairs, which are located in 13 genes coding for proteins, 22 genes coding for tRNA and two genes coding for rRNA.
c) The genetic information is "transmitted from cell to cell, during development of the organism - which, from a single cell, the 'zygote', may, as in humans, hundreds of billions of cells - and throughout life wherever there is a body cell multiplication, for example in the system emopietico. This transmission occurs through the process known as "mitosis." This implies: first, a precise assembly of billions of molecules along each of the two strands of each chromosome that leads to the formation of two copies of "identical" in the original chromosome, called "chromatid" until they are joined by the centromere, and then distributing - extraordinarily coordinated through mechanisms - the two new chromosomes in two daughter cells. In this way, each of them receives the entire set, ie 46 chromosomes, which were in the mother cell.
d) Information Genetics is "spread from one person to another" by cell gametes (oocytes and sperm) which are formed by cells goniali (oogoni and spermatogonia) present in the gonads, through the process of "meiosis". During this process the set of 46 chromosomes is halved, and each gamete is then to have 23 chromosomes, one from each of 23 pairs of homologues. Since their merger will form the zygote, so that will have the full set of 46 chromosomes.
e) The genetic information "varies from individual to individual." This is the consequence of three facts involved in the formation of gametes: i) the number of types gametes possible in each individual, which amounted to 2 23, ie, the value of 8,388,608; ii) the number of "alleles" for a given gene and variants in the noncoding portions of DNA, such as - for example - the 'microsatellite', and iii) the number of interchanges between homologues during meiosis, leading to the recombination of the contents of chromosomes. It follows that the actual number of combinations of genes becomes so high as to exceed any conceivable size of the population. Everyone, therefore, has a "proper genotype, that is its own unique genetic makeup, different from each other. An exception, less than mutative events and a different distribution of mitochondrial DNA, identical twins.
f) The genetic information contained in any single gene "work" by encoding the production of three basic types of molecules that is a model (template ) on which, through complex mechanisms of "transcription", induced by special signals, and "translation", are structured other molecules essential for the life of the cell and the organism. If there are three classes.
the first class belong all the genes-the largest part - coding for the production of mRNA (RNA messenger), that is, specific polynucleotide sequences that represent the "transcripts" of particular genes and are the "mold" in which proteins are synthesized well-defined. These "transcripts", however, before leaving the nucleus are appropriately revised through the process known as splicing by which - with the help of a molecular complex of small nuclear RNA and protein - they are deleted portions of "noncoding" called "introns" and assembled the pieces "coding" called "exons." It is, thus, the final model on which, through a mechanism of translation, which implies the use of two other types of RNA (rRNA and tRNA), formed a specific protein molecule which will have a structural role or function.
the second class belong the genes coding for the production of rRNA (ribosomal RNA), the polynucleotide molecule which is the main component of particles called ribosomes, the structure is extremely important for translating the genetic message carried by mRNA. They are located on the short arm of chromosomes of group D (13, 14 and 15) and Group G (21 and 22) is estimated at 45 and their average number per chromosome.
the third class belong the genes coding for the production of tRNA (transfer RNA), molecule particularly structured to carry a very specific amino acid and its insertion at the right point in the chain during the process of translating mRNA into protein. Their number is about 60, each of which can carry only 20 of a given amino acid involved in the construction of several proteins.
These three classes of genetic information, each with specific tasks, work in a coordinated way. The second and third are active in each cell, the first work in a selective and differentiated into different cell types of the various tissues and organs: that is, all the large number of genes present in every cell are activated only a small part more or less depending on the needs at different times of the life cycle and in different areas of the body. Deserves particular emphasis on the initial phase of this selective activation of transcription. We know today that it is triggered as a result of "signals" through "transmission factors" - proteins in general - come to the core. Under the action of these signals, specific "transcription factors", consisting of protein complexes, into action and, by binding one of them to a particular structure of each gene, called TATA box upstream of the gene itself, open the way to a specific enzyme, a RNA-polymerase, which begins thus to synthesize the mRNA corresponding to that particular gene.
2. The alteration of genetic information. The genetic information contained in any single gene or chromosomes assembled in the can "change." Under the action of physical, chemical or biological, in general these 'mutagens' genes so that the chromosomes can be altered in their structure, undergoing noticeable changes at the molecular level (gene mutations) or microscopic level (chromosomal mutations).
a) gene mutations, also known as "point" . These changes involve alterations in DNA that make up a given gene, the "replacement" of individual molecules, to "deletions" more or less large, to "amplification" of varying length. The consequences are, for the most serious diseases that appear at different times, from the period of embryonic development to maturity and also advanced. 9 April 2000 had already been located in 1549 genes in human chromosomes on which depend many diseases and it is hoped to arrive early to locate those of other already known 3500 (Ú Gene, III). We recall in particular for their high frequency of the gene on chromosome Hungtinton Chorea 4, this complex spinal-muscular atrophy gene on chromosome 5, the cystic fibrosis gene on chromosome 7, the Mediterranean anemia gene to chromosome 11, the myotonic dystrophy gene on chromosome 19, the gene for Duchenne muscular dystrophy in X chromosome With the development of biochemical genetics was possible to demonstrate a good number of them the effect investigation of the gene. It is, mostly, of "enzyme deficiency" that cause the absence of substances needed for proper metabolism and accumulation of metabolites or hypersecretion harmful to the smooth functioning of tissues and organs, as in the case of mucopolysaccharidosis, or a "no or modification of protein Structural and functional specifications, such as in the case of many anemias, and emocoagulopatie dystrophies.
All these mutations accumulate in the population when their effect is not lethal. It is established, then, in them a "genetic load" remarkable. From many researches in order to derive an estimate has emerged: that these errors must attribute the disease from 1:5 to 2:3 people that, on average, each individual brings simple dose at least four genes or groups of altered genes, and that the "genetic load" filed by an average frequency of mutations of the order of 1:10 gametes. It is to these altered genes that are ascribed to many diseases that they feel their weight in families and populations: the inborn metabolic errors numerous, the anemic and hemorrhagic syndromes, hormonal deficiencies, the neuro-myopathy, to the most common diseases - such as diabetes, atherosclerosis and psychosis - in which the genetic component, although more complex to define, is certainly present.
b) chromosomal mutations. They usually involve: a change in the number of chromosomes (aneuploidy), which in man becomes more or less than 46, or an alteration of the shape of chromosomes ("aneusomia) caused by" deletions " or 'translocation'. For the most part these mutations occur and / or occur when the cell is undergoing mitotic or meiotic. When they occur in the "somatic cells" induced disease may be limited - although with very serious events - a cell line or a single organ. One example is chronic myelogenous leukemia, also associated with a reciprocal translocation between chromosomes 9 and 22 in myeloid lineage cells, and similar types of alterations that occur in many forms of leukemia and lymphatic lymph. When, however, are concerned the "germline", ie the error occurred at gametogenesis, then the whole body is concerned with the consequence of serious or severe developmental defects. Just remember: Down syndrome with trisomy 21, Patau's syndrome with trisomy 13, Edwards syndrome, trisomy 18, Klinefelter syndrome (boys) with karyotype 46, XXY, and Turner syndrome ( in females) with karyotype 45, X.
The frequency of these chromosomal abnormalities and diseases that accompany them is not negligible. It is known that 50 to 60% of spontaneous interruptions of pregnancy is due to serious embryopathies caused by chromosomal abnormalities. But, despite this natural selection, among those who come to the birth 1:250 it is still a carrier.
c) gene polymorphisms. Are due to harmful mutations, and occur in different molecular forms of the same gene, called "alleles." Examples are characteristic alleles A, B and O-blood group ABO said, upon which the blood of human subjects in the second allele present in the terminal portion of chromosome 9, and a large number of alleles of HLA (Histocompatibility Leucocyte Antigens ) of extreme importance in the delicate immune systems of the organizations that belong to a family of genes located on the short arm of cromosma 6. Must also remember, for the importance they have assumed in forensic medicine, sequences called VNTR (Variable Number of Tandem Repeats ), consisting of short pieces of DNA repeated after a greater or lesser number of times.
III. The transmission of genetic information
define the processes of meiosis, the formation of gametes and in the presence of these genes, we could deal with rigorous formal methods to study the "transmission model" of individual characters or sections through the generations. There are three main models, already announced by Mendel, which will be exemplified here with data derived from human pathology. Each human body normally takes in his cell, one set of "diploid", made up of 22 pairs of chromosomes, two by two counterparts, known as autosomes, "and two other chromosomes called" eterosomi `in the X and Y, more precisely, two X in females and an X and a Y in the male. Depend on the genes present in the autosomes "autosomal" eterosomi from those in the "characters eterosomici" (X-linked ). The main patterns of "segregation" or "transmission" of the characters are three.
a) autosomal dominant model . The character appears in a person under the influence of a single gene. Whether such a person suffering from Huntington's chorea. It is now known that this severe neurological disease is caused by a mutated gene (denoted by general D) located in the terminal portion of chromosome 4, chromosome 4 on the other hand, this is the normal gene ( d) that - would appear to apparently-inactive, or at least unable to prevent the effect of the allele counterpart: that the subject has genotype ' Dd. To examine how it is transmitted disease in her children, assume the most frequent combination bed, that the person in question to marry a person that both corresponding genes is not changed, ie genotype " dd". The gametes of the subject with genotype Dd lead in 50% D the gene and the gene in 50% of , while the subject with genotype dd would bring all of the gene . From the random combination of gametes at conception would expect these subjects then, of which 50% have genotype Dd and 50% DD genotype . The expected frequency of sick people among the descendants of the combination bed Dd x dd would, therefore, 50% and, respectively, by combining double Dd x Dd the presence of 75% would
b) autosomal recessive model . A given character may appear only if both homologous genes carry the same information. It has, for example, a patient with sickle cell anemia, born of healthy parents: he has altered, both chromosomes 11, the gene (indicated by symbol general r) which determine the production of b chains of hemoglobin . Obviously he must have received the two genes from two healthy parents, but "carry" each have a recessive gene and then with genotype Rr . The law of segregation is clear: taking into account that the frequency gametes with genes respectively R and r from heterozygous Rr are respectively 50%, expect: a combination double Rr x Rr subject rr ("affected") with frequency 25%, subject Rr ("carriers") of 50%, and subject RR ("healthy") of 25%, and the double combination Rr x rr subject rr ("affected ") with a frequency of 50% and subject Rr (" carriers ") with a frequency of 50%.
c) Model eterosomico recessive. A given character may appear only in males when the mother carries the gene in one of her X chromosomes It has such a male subject suffering from Duchenne muscular dystrophy, whose defective gene to which is on the short arm of chromosome X. Obviously can not have received it from his father, as received from the Y chromosome Even if, as is now known, about 30% of cases, the mutation occurred in the maternal gamete is fertilized - and, therefore, not transmitted from ancestors - the risk of getting the disease gene and, consequently, that the posters disease is always 50% for males, while 50% of daughters receive the same gene, but will be "healthy carriers", supplying enough the homologous gene is normally present.
d) multifactorial model. These models - which sometimes, by the action of other "factors modifiers, may give rise to segregation that deviate from the expected - is to add a fourth called" multifactorial model 'or' polygenic '. The manifestation of a given character is here due to the combined action of multiple genes, which is very often associated environmental factors. Suffice it to recall, among the disease, many birth defects that occur in 3-5% newborns, such as central nervous system defects such as anencephaly, spina bifida, myelomeningocele, hydrocephalus, severe heart disease, defects in ventral closure of the line, such as cleft lip and palate, omphalocele, ectopic bladder, and other more frequent, such as diabetes mellitus , atherosclerosis, psychosis and various cancers.
In this model, although individual genetic factors follow either of the models mentioned above, the effects that occur as a result of their combined action are complex and likely to give rise to many "phenotypic classes" in only some of which - in the case of pathological characters such as - see a disease or syndrome, and with what frequency, in general, less than that observed in previous models.
IV. Population genetics and eugenics
1. The genetic structure of a population . For the reproductive processes is always accompanied by the continuous flow of genetic information from generation to generation. Therefore, every human population can be considered as a "reservoir of genes, where each individual who composes it bears his contribution. Then by applying analytical methods, known as 'population genetics' is possible for each of them: a) the frequency of different genotypes, compared to single gene systems and b) frequency of data back to the genes present in it, especially those pathogens. It is these frequencies that represent the "fundamentals" of the genetic structure of a population. To illustrate, referring Mediterranean anemia, it could be established that the defective gene is significantly more frequent in some Italian regions - namely, Sardinia, Sicily, Puglia and Emilia Romagna, where the subjects 'healthy carriers' reach frequencies from 4 , 3% to 24%, varying these frequencies, even from village to village. And in these regions is, therefore, significantly higher frequency of children born with Mediterranean from anemia or Cooley's disease.
Knowledge of the genetic structure of populations have become of great importance not only for the study of "genetic evolution" of populations in time and space and "forces" that continually act on them, such as pressures " selection "and" mutation "and" migration ", but also for the formulation of" epidemiological forecasts "that should be the basis for a preventive medicine of genetic diseases.
2. Genetics and Eugenics . Developments in genetics, which has tried to trace the broad outlines, as well as having opened up new horizons in science and technology to the wonderful achievements of 
continuous advancement in genetic engineering, are increasingly indicating that the genetic information, the which endows all living things of a biological structure is essential to its own being and activity, may have some "flaws" that are reflected in the negative on his state of "welfare" by providing a "medical condition". In the field of plant and animal by a "force of selection," which tends to the elimination of the "pathological". In human, this force - while still working to "natural level" - had to yield to the dictates of a higher power, intelligence and will of which man is endowed, which requires respect and help each person who suffers; This was and still is the task of medicine.
However, the severity of the "genetic disorder" that not only do you feel about the person who is affected, but it reflects on the whole family, which carries the greater load, and the same company, led - especially in the last three decades of the century, under the pressure of the great achievements of genetic engineering - To re-open the way to "eugenics," which seemed permanently closed and put away as a disgrace for humanity after the cruel and serious errors of Nazi Germany. The "genotypic selection," preceded by "prenatal diagnosis" and, today, even "pre-implantation", became the almost unquestioned defensive weapon. It is, in fact, a failure of medicine in the face of humiliating impotence of not being able to do anything for the greater part of genetic diseases, but also a failure in the face of heavy social pressure in which medicine has failed and can not react . Pressure represents a serious "disease of society": a form allergy against a human subject considered "quality not appreciated."
But medicine can react, because it can do a lot - especially today, to "prevent". This is the greatest challenge of modern medicine, and commitment it must take when you can not treat and cure. This is the "eugenics ethically correct," which will be valid even when advances in genetic engineering will - hopefully - open treatment options for many of these diseases. An essential requirement to meet this new responsibility of medicine is now the "information" to provide people who are at risk of these diseases for themselves or their families. Information that constitutes the fundamental part of the so-called "genetic counseling".
V. Genetics and Medicine
The "obligation" of this advice was recognized at the first International Conference on Prenatal Diagnosis in David (Quebec) in 1979 (see J. Hamerton, N. Simpson, Prenatal diagnosis: Past, Present and future. Report of an International Workshop , "Prenatal Diagnosis" 1980, 1, Special Issue, 1-57). For Italy was reaffirmed in the document Prenatal Diagnosis, published by the National Committee on Bioethics July 18, 1992 (Rome, 1992). Indeed, in that it stressed "the importance of ethics and character," noting that "the implications of personal and socio-medical importance of the interview with the consultant [...] give the genetic counseling on the characteristics of the doctor's regardless of subsequent diagnostic indication. "
The "need" for such advice, and preparation of medical need for it, has become even more pressing today. The underlined CT Caskey, President of American Society of Human Genetics (ASHG) and Human Genome Committee of the Company, in a letter dated December 28, 1990 to J. Watson, then director of the National Center for Research on Human Genome to National Institutes of Health (NIH): "The members of the ASHG deal with these issues every day in their role as physicians, genetic counselors and laboratory directors, providing sensitive information and highly personal to the future health of the individual and the family. [...] There is need for extensive research to define in advance the exact nature of the problems, and training programs to prepare experts for legal and ethical decisions in the field of medical genetics' (ASHG Human Genome Committee Report, The Human Genome Project: Implications for Human Genetics , "American Journal of Human Genetics 49 (1991), pp. 687-691).
This "medical procedure" has several moments, each with a certain purpose, and all important information for the purpose of good and responsible family. We refer here especially when obligatory meeting with the doctor - though often neglected or carried out in an irresponsible manner - by a family at risk in view of a prenatal diagnosis (PD). But many signs of relevance to any genetic counseling in view of diagnostic tests and prognosis.
1. Verification of the existence of a "claim" to the DP . The situations of a "claim" is substantially reduced to two: a) significant increase in the risk (more than 1%) of a chromosomal aberration embryopathy in pregnancy, and is, precisely, the increased risk that all women who conceive over 37-38 years of age, and b) parents who are carriers of mutated genes phenotypically autosomal dominant or recessive, or eterosomici, involving high risks to 25-50% for each pregnancy that the subject manifests more or less quickly disease, in general, very serious: these situations authorities that are increasing with the progress of the Human Genome Project. The importance and sensitivity of this first step today require a great responsibility, and above all we must emphasize the serious abuses that, even under the pressure of commercial interests, were introduced into medical practice with so-called "predictive text" behind the which hides a well-defined and declared intention eugenic.
2. Decision on the feasibility of a given diagnosis and the diagnostic information . It is a necessary condition for the indication can be implemented. When there is an indication, and the woman or the couple - after further consultations - would like to proceed with the diagnosis, one must decide whether it is "feasible" or not. To meet this need, which will grow with increasing knowledge about gene mapping, are needed by the doctor for a consultation ethically correct, a continuous update on the diagnostic possibilities relating to the case of sites where knowledge can be done the necessary research.
is a need for ethics, because it depends on the decision of applicants to perform or not the diagnosis is fully "informed and free." A recommendation Council of Europe 1991 (The depistage génétique antenatal, antenatal and génétique diagnostique the conseil génétique y relatif, "International Journal of Bioethics 1 (1991), pp. 13-22) expressly states:" The informed consent is required even if genetic tests are applied systematically. The systematic nature should not be considered under any circumstances connected with that of obligation. The systematic means that tests can be offered to pregnant women where there is a valid reason scientifically in doing so. [...] The information given to women in the counseling sessions must be suitable for their level of education and its psychological state so that she can easily understand the information and make a decision on an informed basis. "
This is more challenging phase of the consultancy. This is not to impose the steps to perform, but to help the woman or couple to make a decision whether to run or not prenatal diagnosis. It involves the person of the physician more than it does a simple "medical examination", because it must accompany the applicants to their own choice. In the interview, which generally occurs for many reasons with people who live in a particular state of tension, should appear clearly: the difficulties you may encounter, the risks, especially to the fetus, depending on the method used, the risk of a dreaded disease to the fetus, the nature and extent of the disease, the uncertainty that may remain in the definition of results, the odds or at least the possibility of errors, eventually leaving open the availability for further clarification.
3. Accompanying applicants. Anxiety and anguish arising in anticipation of a patient with a serious disease are natural reactions. As long as a DP, even if the prevailing sentiment when they are done well the first three times, is that of hope and confidence, the fear that a particular risk - albeit small - occurring just in case of applicants is always present. And fearing the question arises which places the woman and the couple in front of the dramatic choice between two options: keep the child even if it will bring pain and suffering to the family, or not to accept it. It is a disturbing conflict, compounded by strong social pressure towards the non-acceptance "and little or no help from family and friends. Your doctor may do much to restore a state of greater calm, giving complete and accurate information on the dreaded disease or malformation, the real possibility of recovery or low probability of survival. However, it is above the underlying thought inevitably of a possible "voluntary interruption of pregnancy" that creates the most difficulties in processing. Understanding and respect for the thought of applicants, regardless of personal views of the doctor, and will ensure that it will not break the cozy relationship and trust needed in this very delicate situation, will also offer real help, not to give or push a decision corresponding to their belief, but to make it less painful to the period of waiting for the diagnosis and mature by the pair, a decision - whatever it will be - more aware and less traumatic.
4. support in case of unfavorable diagnosis . The medical procedure can not stop "before the diagnosis." Must continue, he becomes "essential" in cases where the results indicate the presence or anticipation of a dreaded disease, trying to help - especially the woman-in the work of the excruciating decision on the fate of her child, knowing also include all the tension rejection, and not abandoning - indeed Stand closer, if possible - when it will pass through the period shorter or longer or more less severe depression as a result of what may have happened.
The great advances in genetics have opened and are continually expanding the spaces of "genomic revolution", from which they expect substantial benefits for humanity. Many will come from the great technological applications in agriculture and livestock, but will be core applications that are maturing in the field of medicine. Medicine as a profession, particularly the prenatal and perinatal medicine, shall be the responsibility of the serious responsibility. First of all, to not declare the fact of his impotence in the face of patients - particularly embryo and fetus - which, perhaps for a long time to come, will be difficult to treat. It will be responsible, however, to meet as much as possible to those who need to have professional assistance and human: a) trying to develop a scientifically sound and pedagogically valid "primary prevention", which will decrease the need for recourse to prenatal diagnosis; b) using the "new medicine" as the progress of gene therapy will offer a real possibility, and c) when all this could be feasible, accompanying and supporting, with a true sense of solidarity, the woman and family in their distress and in their suffering. This is part of the code of medical ethics whose foundation, yet at the end of the first half of the twentieth century, K. Jaspers summed up: "The doctor is not a technical nor a healer, but a life in the service of another life" (D. Von Engelhardt, History of medical ethics, in S. Leone, S. Privitera , Dictionary of Bioethics , Bologna 1994, pp. 954-958).
In this way, the medicine, while accepting the challenge of the approximately 4000 genetic diseases and chromosomal pathology relentless and elusive for a long time - if not always - require the use of prenatal diagnosis, will help in his position of authority a restituire alla società e a conservare in essa il vero senso della maternità e della famiglia.
Bibliografia:
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