Biotechnology (from the Greek βίος, bìos = “life”, τέχνη, téchne = “art”, in the sense of “expertise”, “knowing how to do”, “knowing how to operate”, and λόγος, lògos = “study”) is a new and sometimes controversial branch of biology concerning ’the use of living beings in order to obtain goods or useful services to satisfy the needs of society,’ but also the application and study of any technology developed or developable by the man to the field of biology.
Innovative biotechnology dates back to 1928, when the British physician Frederick Griffith, experimenting with a vaccine against streptococcus pneumoniae, observed that these microorganisms are able to acquire and maintain “hereditary material” from other bacteria and transform themselves. Since then, researchers around the world have been working to identify what lies behind the mysterious “transformation factor”.
Griffith is considered the father of genetic engineering: scientist of great intuition, in those years he could not know that that hereditary material was, in fact, constituted by DNA. The actual discovery took place in 1944. And in 1953 was discovered the structure of DNA and its replication mechanism. The birth of genetic engineering is, finally, something of our days and will mark a clear distance between traditional biotechnology and innovative ones.
The various techniques used in biotechnology are:
- Recombinant DNA. It consists in extracting DNA from the cell of an organism, isolating the genes of interest and inserting them, with or without modification, inside cells of different organisms. In this way it is possible to overcome the natural biological barriers between different species, artificially modifying the genetic makeup with the insertion of foreign DNA.
- Combinatorial Chemistry. It consists of a set of techniques that, anchoring on a surface many molecular alternatives, allows to obtain in parallel many chemical reactions. In this way, the same substance can be made to react with different molecules. This makes it possible to identify a particular compound within a large set of products.
- Antisense technology. This is an application that allows nucleic acids to be acted upon in order to inhibit the manufacture of proteins. By inserting ribonucleic acid (RNA) molecules or antisense DNA strands into cells, the molecular sequence by which a given gene is expressed as a protein is interrupted. This technique is showing promise in the treatment of genetic diseases, infectious diseases, and cancers.
- Genetic engineering. set of techniques that allow to modify the characteristics of organisms. They aim to detach a gene from the genome of an organism and insert it into that of another in order to obtain, for example, bacteria capable of producing drugs, to modify viruses and bacteria and make them capable of transferring to plants and animals foreign genes that improve their characteristics, to produce animals “humanized” organs that can be transplanted into humans, to insert in human cells “healthy” genes in place of defective ones responsible for about 4 thousand hereditary diseases (gene therapy).
- Cloning: technique that allows you to create an identical copy of an organism. To clone an animal, for example, you take from the tissues of his body a single somatic cell from which you extract the nucleus with all the genetic material it contains. It is then transferred to an egg cell, deprived of the original nucleus, from a female of the same species. The egg thus modified is implanted in the uterus of the female who will give birth to a clone, that is a faithful copy of the animal of departure.
- Biolistics: method that takes its cue from the fusion of the words “biology” and “ballistics”, as it bombards the cells of plants to be modified, usually monocotyledons such as wheat, corn and rice, with tiny beads of gold covered with genes that you want to insert. The surviving cells that have managed to acquire the new genes will give rise to transgenic seedlings.
Applications of biotechnology in pharmacology
Important drugs can be produced with biotechnology. Early biotechnology drugs include human insulin (1979), followed by growth hormone (1985), interferon, and blood proteins (1987-1989), such as erythropoietin (EPO), the molecule that controls red blood cell production. Coagulation factor VIII was also obtained in the laboratory, thus solving the problem of safe blood products for the treatment of hemophilia. Modulators of the immune system have also been developed (1986-91).
Thanks to biotechnology it was also possible to isolate the virus responsible for AIDS and to develop the first drug used against the disease, AZT. Other drugs have been developed with biotechnology, such as interferons-alpha-2a, 2b and n3, OKT3 anti CD3 against transplant rejection, tPA for cardiovascular diseases, GM-CSF active on bone marrow transplant recipients, G-CSF for cancer chemotherapy, factor IX antitumor, pulmozin for cystic fibrosis and cedrase for Gaucher disease. Biotechnological drugs, being synthesized by bacteria on the instructions of a gene extracted from the human genome, are more specific, cost less, because bacteria reproduce quickly and are more pure, i.e. they have a much lower probability than traditional drugs to transmit virus infections.
Today the main tool used by biotechnology is genetic engineering. There are at least a dozen branches of biotechnology, most of which are usually identified in international language with one of the colors of the rainbow. Red: is the field of biotechnology that deals with biomedical and pharmaceutical processes for the identification of active ingredients and vaccines; Green: is devoted to agricultural processes (eg. for the realization of GMOs); Yellow: is interested in the production of special foods (gluten free, light, lactose free); White: focuses on industrial biotechnology; Grey: is dedicated to environmental protection and preservation; Blue: is dedicated to studies on marine organisms; Gold: develops bioinformatics and nanotechnology; Black: is engaged in the study of bacteriological weapons; Violet: focuses on ethical issues related to biotechnology; Orange: works for the dissemination of biotechnology studies and discoveries to the general public.
Medical biotechnology is the branch of biotechnology dedicated to the discovery and development of active ingredients, the production of vaccines and the development of new techniques for the analysis and diagnosis of diseases and related gene and cell therapies.
More specifically, they see the application of biochemistry, microbiology and genetic engineering for the production of goods and services in the medical-pharmaceutical field, for the diagnosis and treatment of diseases.
In particular, in the diagnostic field – thanks to the progress of genetic engineering – biotechnologies have achieved important goals, contributing to an increasingly early and specific diagnosis, which has become of fundamental importance for any kind of pathology, but especially for complex diseases, chronic diseases and cancer, whose onset is not necessarily attributable to a single cause, but is due to the delicate combination of environmental and genetic factors.
The application of biotechnology in diagnostics is therefore leading to the development of increasingly accurate and less invasive methods for the identification of a particular disease state, moving more and more towards predictive and personalized medicine. The objective is a more precise definition of the diagnosis, thus having the possibility to implement targeted medical treatments, ad hoc.
Applications of biotechnology in agriculture
The application of biotechnology in agriculture could allow an increase in production without the need for massive use of land, labor and capital, as well as decrease or abolish the use of chemical fertilizers, herbicides and pesticides that have so damaged the environment to date. Among the most common methods to introduce into plant cells genes from other organisms or artificially synthesized is the use of the bacterium Agrobacterium Tumefaciens, which normally carries a plasmid containing a gene capable of inducing tumors in plants: this gene is replaced with the one carrying the desired character, the plasmid is then reinserted into the bacterium that infects the plant cell and transfers the DNA. An alternative to this method is to “shoot” DNA fragments wrapped in tiny metal capsules directly into the plant cells. In both cases the plant cell incorporates the DNA into its genome, and then generates whole plants, carrying the new gene and therefore the new character.
The main characteristics that can be acquired by plants through the insertion of a foreign gene and interesting from a commercial point of view are resistance to pathogens, resistance to herbicides and resistance to environmental stress. Resistance to viruses and bacteria, which can make the plant sick or even die, and which cause considerable losses to agriculture, is an extremely important characteristic. In fact, the traditional methods of prevention and treatment, such as crop rotation and the use of chemicals able to limit the infection by these pathogens, have been only partially effective and, sometimes, harmful for the environment.
The first genetically modified plants able to resist viral infections were obtained around 1986, thanks to the insertion of the gene responsible for the synthesis of the protein that forms the viral envelope itself: the plants equipped with this protein, in fact, showed resistance to the virus wrapped in that same protein. This means, clearly, that resistance cannot be conferred against any type of virus, but towards a specific virus, possibly the most specific and harmful for each particular type of plant. Genetic engineering has also succeeded in conferring insect resistance to some plant organisms using a particular gene taken from the bacterium Bacillus thuringiensis. This bacterium was already used as a biological insecticide, because it is able to inhibit the functionality of the digestive system of insects, and therefore to poison them. Its capacity is given by the presence of a gene that encodes for a toxin: to insert this gene in the vegetable chromosomes means to give directly to the plant the possibility to kill its own parasites. Moreover, it has been demonstrated that this toxin is not harmful either for the plant that produces it or for those who feed on it, as it acts only against some proteins typical of insects.
Thanks to these techniques it has been possible to generate maize resistant to the corn borer, a voracious butterfly that, at the larva stage, devours the stem of the plant. The modified maize has been subjected to careful analysis before being put on the market and Italy, despite having authorized its importation at the beginning of 1997, has allowed its cultivation only afterwards. Also climatic conditions have a fundamental importance both on the quantity and on the quality of agricultural products, and scientific interest has been focused on the biochemical and genetic basis of the response of plants to environmental stresses such as cold, drought or salinity variation. It was thus highlighted that there are systems common to many types of plants related to the expression of a few genes.
In March 1999, a group of Japanese researchers demonstrated that by suppressing the activity of a single gene that is normally activated in response to environmental stress, it was possible to make a transgenic Arabidopsis plant resist cold. This organism shows a growth and production fully comparable to that of unmodified plants, but has the ability to resist without water for two weeks, at high salt concentrations and temperatures below 0 ° C for two days. The presence of some genes that actively confer resistance to environmental stresses has been highlighted, and experiments of genetic transformation have made possible the birth and development of plants that, having acquired these genes, are able to respond by protecting themselves from adverse conditions; research in this field are now directed towards plants of agricultural interest.
Weeds are a serious problem for crops: their presence can take away water, nutrients and light from the cultivated plants, sometimes strongly reducing their production; moreover, in order to be separated during the harvest, weeds require a greater work and economic commitment. Until now, weeds have been combated with herbicides: each herbicide used had to be directed specifically against a particular weed, so as not to damage the cultivated plant; the presence of multiple weeds in the same crop, therefore, required the use of multiple herbicides, with significant economic and environmental consequences.
Genetic engineering has made it possible to confer resistance to herbicides to the plants of interest through two alternative mechanisms: either they become able to inactivate these substances, or they present a modified form of the enzyme targeted by herbicides, becoming insensitive to them. It is therefore possible to use less specific herbicides with a greater range of action in order to obtain a pest control action that is completely effective and harmless to the crop. An example of this technique is given by the soybean made genetically resistant to glyphosate, the active ingredient of many herbicides that is able to inhibit an enzyme vital for all plants. The genetically modified soybean contains a bacterial gene that confers resistance to this herbicide, and was carefully analyzed before being placed on the market, to ensure that the desired change did not generate other, unexpected changes; that the genetic change was stable, that is, heritable, and that the gene introduced could not be transferred from one individual to another according to unforeseen mechanisms.
Detailed molecular analyses have shown that the genetic modification does not generate further changes, especially with regard to the synthesis of new allergens, which is stable through several generations and is not transferred to other organisms. Moreover, the substance produced has characteristics that make it extremely attractive: it is harmless to animals and rapidly decomposes into non-polluting residues.
Great efforts of genetic engineering are also directed towards the improvement of the nutritional properties of plants and to obtain the production of substances of industrial interest. One of the most studied and discussed results has been that of the Flavr Savr tomato that, thanks to the presence of a non-functioning gene, rots in a much slower time than the natural tomato. This allows the maintenance of the product for a long time, also facilitating its distribution.
As it was experimentally necessary to insert, together with the non-functioning gene, a gene responsible for the resistance to a particular antibiotic, this product did not obtain a great consensus: in fact it was feared that the resistance to the antibiotic could be passed from tomato to some bacteria, or even to the consumer, with evident harmful consequences. Later on, this fear has been removed, as it has been demonstrated that the gene for antibiotic resistance undergoes a rapid degradation.
Other results of biotechnology applied to agriculture have led to the production of seedless grapes, strawberries resistant to cold, melons able to use sea water to survive, potatoes that do not absorb frying oil. An interesting application has the aim to accumulate in the leaves of legumes, rich in essential components of food and used in all countries, the important proteins that normally are deposited only in the seeds. Biotechnologies applied to agriculture represent a considerable source of income, and therefore they have attracted the attention of many private companies that base their activity on the development of these researches.
Industrial biotechnology involves the use of living cells or their components for the production of goods and services aimed at greater environmental sustainability in industrial production systems.
They present a rich range of applications and the number of sectors in which they can be used is increasingly wide. In particular, their use in the production of chemical products is still at an early stage, while the prospects of industrial biotechnology are very significant in the field of polymers – i.e. molecules with high molecular weight – where the use of biotechnological process allows to eliminate, for example, the use of sulfuric acid, thus producing less waste and presenting lower energy costs.
Of great interest is the specific segment of the synthesis of biodegradable polymers, in which polylactic acid, produced since 2002 by means of fermentation from starch, has properties similar to conventional polymers, but is completely biodegradable.
With regard to consumer products, industrial biotechnology has made it possible, for example, to reduce the environmental impact of detergents by replacing phosphates with citric acid, which is just as effective, but completely biodegradable, non-toxic, low-cost and produced by fermentation from renewable sources. We should also remember that, thanks to the use of enzymes in detergents, it is possible to wash at lower temperatures, with consequent energy savings.
The birth date of biotechnology can be traced back to 1857, when Louis Pasteur described the mechanisms behind leavening and fermentation. Other historic dates were 1878, with the discovery of leavening enzymes, and 1929, with the recognition of enzymes as proteins. Further steps forward were the researches on heredity conducted by the monk Gregor Mendel (1856-1866), the demonstration of the process of bacterial transformation (1928) and, finally, the discovery of the structure of the genetic code by James Watson and Francis Crick (1953).
A long journey in which the ground was prepared for what constitutes the decisive push to the development of biotechnology: the development, in 1973, of the technique of recombinant DNA, which opened the way to genetic engineering. Since then, biotechnology has entered a new phase of development, that of so-called innovative biotechnology, with results in the fields of pharmacology and medicine, agriculture and food.
In the field of tissue engineering biotechnology has made enormous progress: epithelial cells, cultured on an artificial biocompatible support, such as hyaluronic acid, and then stimulated with appropriate growth factors, reproduce quickly allowing transplantation of human-like skin. In industrial microbiology it is possible the production, in microorganisms, of proteins typical of other organisms but in controlled quantity and modified in their structure to increase their functional value. Innovative developments also concern the processes of fermentation, bioconversion and biodegradation for the disposal of municipal and industrial waste, always through the use of specific microorganisms.
In agriculture, thanks to new biotechnologies, the production of plant species resistant to pathogens and herbicides, able to use atmospheric nitrogen, able to produce seeds with high protein content and better quality, resistant to unfavorable chemical and climatic conditions has improved. In the field of bioinsecticides, traditional chemical products that are highly polluting and harmful to humans and animals have been replaced by the use of both new substances produced by microorganisms, and biologically manipulated microorganisms with insecticidal activity, to protect plant crops from pests (bacteria, fungi, viruses). In medicine, biodiagnostics has also benefited from new biotechnologies, in particular for the production and widespread use of monoclonal antibodies. These are in fact used for in vitro and in vivo assay of proteins, hormones, drugs, viral antigens, bacterial and associated with neoplasms, as well as for the localization of tumors and metastases even of small size.
Monoclonal antibodies have been used experimentally in cancer therapy, to selectively deliver toxins and chemotherapeutics to tumor cells only. Gene therapy has also benefited from new biotechnologies. They are now possible, in fact, the insertion of a specific gene in an organism, in order to restore a function that may have been altered originally or totally missing from birth; the use of animals as “bioreactors”, ie the creation of transgenic animals capable of producing pharmacologically active substances that the animal does not produce naturally; the development of vaccines no longer based on the entire microorganism (killed or weakened) but only in its non-infectious genetic components, able to trigger the immune reaction from the body. Finally, the development of biotechnology has made it possible to improve the techniques of fertilization and in vitro growth of embryos and their subsequent reimplantation in the uterus.