What are bionics and biotechnology?

Indications and Procedures

Bionics and biotechnology are part of the larger arena of
bioengineering. This broad interdisciplinary field integrates the many disciplines of biology, physics, and engineering for use in the medical sciences, as well as in other areas such as agriculture, chemical manufacturing, environmental studies, and mining. Because of the interdisciplinary nature of these studies, an often-confusing array of terms may be used, such as biochemical engineering, bioelectronics,
biofeedback, biological modeling, biomaterials, biophysics, biomechanics, environmental health engineering,
genetic engineering, human engineering, and medical engineering. When applied to the medical sciences, these various areas of knowledge can be integrated under the headings of bionics and biotechnology when considering the diagnosis, investigation, prevention, or treatment of diseases and damaged biological
systems.

Within the medical sciences, bionics is concerned with applying physics and engineering concepts and methodology to constructing artificial systems, such as organs or limbs, in order to replace damaged or diseased natural systems. To duplicate biological systems and replace them successfully, knowledge of how these systems function biologically, chemically, and mechanically is required. Creating artificial systems has evolved from the making of crude imitations, such as an artificial kidney machine, to the making of sophisticated replicas of the natural system, with the replacement being made in the living organism. While it is necessary to apply physics and engineering knowledge to duplicate these natural systems, the fact that these are natural systems requires the application of biological knowledge to the engineering effort. Some animals have the ability to regenerate lost or destroyed limbs; humans, however, must rely on their ingenuity. Biotechnology is an interdisciplinary field that seeks to replace, if not re-create, nature.

Within the medical sciences, biotechnology is concerned with the manipulation and study of biological systems at the molecular and genetic level. In addition to a basic understanding of how these systems function at these levels, biotechnology is used for practical purposes as well, including noninvasive diagnostic methods, cardiovascular measurements, bio-optics, medical imaging, modeling in physiology, and microsurgical techniques. A significant application is the synthesis of biological products, such as antibiotics, biochemicals used in diagnostic tests, drugs, enzymes, vaccines, and vitamins. This field is also concerned with the manipulation of genetic material to improve this synthetic process, as well as the study of
genetic diseases and the manipulation of the associated genes to prevent or cure these diseases. These kinds of syntheses and studies involve the use of molecules, cells, or genes as raw materials in biological processes that are duplicated under artificial conditions in order to improve or increase the quantities of needed biological products. The techniques and methodologies used to achieve these results are the basis of
the technology. Thus, once again, a thorough knowledge of biology and engineering is needed to understand the natural system and to improve the process by which the natural system works in order to accomplish an imposed artificial result.

Much of this work has been carried out through the use of recombinant DNA technology. Since genes provide the instructions controlling those processes by which biological products are made, it is possible to change the processes, or the rate of the processes, by changing the genes. Through genetic engineering, cell cloning, and other techniques, it is possible to make naturally produced antibiotics, vaccines, vitamins, and other needed biological products rather than duplicating these products with artificial materials using artificial means. Also, the rate at which these products are naturally produced can be increased so that large quantities can be obtained (under natural conditions, these products are produced in extremely small amounts). Another aspect of recombinant DNA technology has to do with diseases that result from biological processes that are improperly controlled by genes at critical points. Genetic engineering is used to replace or correct the genetic structure in order to replace or correct the instructions used to guide the biological process.

There is still much to be learned about biological processes and about the genetic material. It is estimated that there are about 100,000 genes constructed from some 3 billion base pairs. Discovering how these genes interact and the biological processes that each controls is a formidable task. By 2003, the
Human Genome Project had successfully mapped the entire human genetic structure from which all biological processes are controlled, including the flawed ones that cause diseases. Eventually, studies of other genomes, such as those of bacteria and viruses, will treat or prevent diseases and illnesses caused by them as well. This study of genetic material and the use of the tools of proteomics, whereby proteins produced from this genetic material are identified and their functions are elucidated, along with the ongoing study of genetic diseases and of other diseases at the molecular level, will have an increasingly important impact on the overall diagnosis, prevention, and treatment of diseases.

Biotechnology has contributed much to the medical sciences in a relatively short time. It has provided a better understanding of human physiology and an improved fundamental knowledge of disease itself. Knowledge has been gained about the physiological control networks (in part resulting from related studies in cybernetics), the key regulatory agents and processes, the target molecules needed for therapeutic intervention, and the molecular and genetic causes of disease.

With rapid advances in biotechnology, however, the scientific and medical professions are entering sensitive and controversial areas that have raised legal and regulatory concerns. The alteration of genes, the creation of modified organisms, the development of new drugs, the safety and side effects of new biochemicals, the detection of genetic diseases in the fetus, experimental therapies, the ability to clone, the ability to enhance brain functions, and the national and international competition to produce pharmaceuticals are some of the concerns facing medical practitioners, the biomedical industry, government, society, and the individual. These concerns will escalate as biotechnological advances delve even deeper into the molecular and genetic basis of life in order to achieve improved health benefits.

Uses and Complications

Most of the applications of bionics have been centered on replacing damaged or diseased natural systems. Bionic implants, either in development or commercially available, include retinal implants, urinary implants, cochlear implants, hippocampus replacements, larynx implants, and advanced hand replacements.

The learning retinal implant system includes an implant that replaces the function of a defective retina in individuals with retinal degeneration, including, for example, those with retinitis pigmentosa and macular degeneration. A normal retina includes cells that are stimulated by light to produce a signal that is transmitted to the brain and converted into a visual perception. When such cells do not function, vision is affected. A relatively system includes a retinal stimulator implanted in the eye, a pocket processor, and glasses that contain a small camera. The processor includes a microcomputer responsible for translating image data into retinal stimulation commands. Initial studies with four patients using a prototype system, which included all the above components except the camera, have been positive in that the patients were able to see light as well as simple patterns.

The urinary implant is an implantable pacemaker for the bladder. It will be marketed for bladder dysfunctions caused by spinal cord injury. The device allows for urine storage and full bladder control without the use of catheters.

The cochlear implant

is commercially available and consists of an implant that delivers electrical signals to an electrode array. Unlike hearing
aids, which act to amplify sound, the cochlear implant sends sound signals directly to the auditory nerve, thus bypassing the damaged portion of the ear.

A neural interface system is being developed that allows severely motor-impaired individuals to communicate with a computer through their thoughts. The system includes a sensor that attaches to a portion of the brain
and a device that analyzes brain signals. The signals are translated and allow an individual to control a computer cursor. In the future, it is hoped that the device will allow an individual to control other devices, including lights, telephones, and television sets.

Yet another brain implant being developed is a hippocampus replacement. The hippocampus is a portion of the brain that is important, among other things, in learning and memory; it is the first portion of the brain damaged in Alzheimer’s disease. The silicon hippocampus replacement is considered the first prosthesis to replace a damaged area of the brain. In 2007, it was tested in rats, and tests in humans were projected to take place sometime in the near future.

A further application being developed is the implantable artificial electrolarynx

communication system. The system is designed for patients who have had a complete laryngectomy. Approaches will be used to attempt to approximate normal voice and speech production.

The Cyberhand Project is developing a cybernetic prosthesis that is controlled by brain signals. Therefore, the hand will allow amputees to use their thoughts to move it and use it to grasp objects naturally. Additionally, the user will also be able to feel objects with which the device comes in contact.

While there are many applications of biotechnology, some of the more significant ones include the production of pharmaceuticals and biochemicals, the production of monoclonal antibodies, the improved understanding and control of complex diseases such as cancer and Acquired immunodeficiency syndrome (AIDS), and the improved understanding of genetic diseases. Many of the biotechnology techniques and methodologies are still experimental, as are the resulting products (for example, antibodies, drugs, enzymes, vaccines, vitamins, cloned cells, and recombinant DNA). Some are considered useful and practical, but are not yet approved for use.

The production of pharmaceuticals and biochemicals has been one of the most practical outgrowths of biotechnology research. It has produced both the knowledge of what needs to be done to correct a certain disease process and the ability to make the needed corrections. Some diseases result from deficiencies in particular proteins, as is the case with diabetes, hemophilia, and dwarfism. Others result from deficiencies in enzymes that would normally break down other chemicals, thus resulting in an accumulation of these chemicals, such as in Fabry’s, Gaucher’s, and Tay-Sachs disease. Still others result from a lack of cellular control, such as cancers.

It has been possible to produce proteins (insulin for diabetes, factor VIII for hemophilia, and growth hormone for dwarfism), enzymes, and bioregulatory proteins (interferon for cancer). This is done by learning how these proteins are produced naturally and then engineering the cells or biochemical processes that can produce these proteins in quantity. In addition to these various kinds of proteins, other biochemical products can be made, including antibiotics, vaccines, and vitamins. Scientists may produce natural, unaltered biochemicals; altered biochemicals (for improved results); or synthetic versions of the biochemicals.

Monoclonal antibodies are a significant group of naturally produced, unaltered biochemicals. They are highly specific biochemicals used for the diagnosis of infectious diseases, for monitoring cancer therapy, for determining the blood concentrations of therapeutic drugs and hormones, for use in some pregnancy tests, for suppressing immune responses, and, to some extent, for disease therapy (for example, to kill cancer cells). Examples of monoclonal antibodies that have been approved by the Food and Drug Administration (FDA) include those used to treat transplant rejection, macular degeneration, multiple sclerosis, inflammatory diseases (including inflammatory bowel disease, rheumatoid arthritis, psoriasis, and allergy-related asthma), and a wide variety of cancers (including non-Hodgkin’s lymphoma, breast cancer, acute myelogenous leukemia, chronic lymphocytic leukemia, colorectal cancer, head and neck cancers, and non-small-cell lung cancer). While much of this work is still experimental, there is a great potential for the development of highly specific
vaccines and for reagents used in diagnostic tests. In addition to being highly specific, these vaccines and reagents would be free of any biological contamination and tend to be reliably stable at room temperature. The vaccines would also be safer since their production would not require the handling of large quantities of the pathogenic agent (which is how vaccines have traditionally been obtained). Possible uses could involve immunological protection against hepatitis B, herpes simplex, polio myelitis, rabies, and malaria.

Molecular pharmacologists also develop biochemicals from nonhuman sources. In fact, the diversity of animal and plant life in the world is a natural pharmacy of potentially useful biochemicals. Many medicinal plants are already known, and systematic studies of other species are under way. Animals also contribute useful biochemicals. For example, excretions from the skin of tropical frogs have been used to treat skin diseases, diabetic ulcers, eye infections, and cancers. Through the study of fifty species of poison arrow frogs, scientists have discovered more than three hundred chemicals. Biotechnology has made it possible to study natural biochemicals in small amounts and at the molecular level and has provided the necessary techniques and methodologies for using these biochemicals in the study of diseases.

Cancers form a complex group of diseases that continue to defy the best attempts to understand them. A cancer is composed of cells that have proliferated uncontrollably. This response may be caused by a mutated gene, by carcinogenic agents (for example, chemicals or ultraviolet light), or by viruses. Cancers develop in multiple stages that involve different physiological mechanisms. Understanding these mechanisms and the genes and biochemicals that are involved has been possible in large part because of the techniques and methodologies of biotechnology research. Gene therapy is showing great promise for curing some types of cancer.

The same can be said of the efforts to study AIDS. This syndrome is caused by a virus that infects and kills certain kinds of T lymphocytes that are needed to initiate and maintain normal immune system responses; therefore, AIDS is characterized by the occurrence of unusual infections or by Kaposi’s sarcoma (a rare cancer). The nucleotide sequence of the viral genome has been determined through recombinant DNA technology, and the functions of the genes are being characterized. Diagnostic tests to determine if blood is contaminated by the virus have been developed, and efforts are under way to develop a vaccine. The proteins used in these immunological investigations are made in large quantities by genetically engineered microorganisms. Other vaccine studies are concerned with using recombinant DNA technology to disable the AIDS virus genetically (by removing or altering its genes) so that it will
infect and generate protective immunity without actually causing the disease.

Genetic diseases are also beginning to be understood as a result of biotechnology. Many of these diseases are caused by gene mutations that cause the absence of a protein or the production of a defective protein, affecting biochemical processes. Recombinant DNA technology is providing methods of detecting these defects, as well as providing therapies for correcting or replacing them. Many of these defects can even be diagnosed in the fetus and in previously undetectable carriers. Some of the commonly known genetic diseases include Alzheimer’s disease, cystic fibrosis, hemophilia, Huntington’s disease, muscular dystrophy, sickle cell disease, and thalassemia. There are approximately three thousand genetic diseases resulting from single-gene mutations. In addition to studying these numerous mutations, efforts are being made to study diseases associated with specific normal genes (such as the susceptibility for heart attacks by individuals with genes producing specific cholesterol-carrying proteins) and to cure genetic disorders by replacing the mutated gene with a normal gene. This normal DNA acts as a template for production of a certain type of ribonucleic acid (RNA), messenger RNA (mRNA), which acts as a template for production of the normal protein.

One advantage of learning more about common genetic diseases is that more can be learned about normal genomes by comparing them with mutated genomes. These diseases are few in number, however, and much remains to be done. With a map of the human genome (as well as the genome of other animals, plants, bacteria, and viruses), biotechnology, and its usefulness to the medical sciences, will advance significantly. The Human Genome Project has essentially produced a map of the entire human genetic structure, including every gene in the twenty-three chromosome pairs. This accounts for about 100,000 genes with about 3 billion base pairs. In addition, there are about 3 million differences per genome from one individual to another. These differences are responsible for such things as personality differences and inherited diseases. To find and understand some of the rarest disease-causing genes, it is estimated that the differences between the genomes of some 4 billion individuals will need to be studied. This resulting database would strain even state-of-the-art computers, not to mention the researchers who will compile the database.

Study of the differences between the genomes of individuals, and in particular the differences in genes involved in drug metabolism, will be a starting place to provide researchers with a way to overcome adverse reactions to drugs from selected portions of the population by applying the tools of pharmacogenomics, the study of how a person’s genetic makeup (genotype) affects the response to drug treatment. After correlating the differences in the genes with a specific negative response, researchers will then need to determine the genotype of a specific individual and use that information to determine the treatment regime that will be most effective for that individual. Alternatively, such information will allow drugs to be developed that are customized for the population to which the individual belongs.

Although many therapeutic strategies involve replacing a mutated gene with a normal gene, other strategies that are currently being developed use short pieces of DNA, called oligonucleotides, to correct the underlying mutation in the DNA of an individual. For example, single-stranded oligonucleotides that include the correct sequence of nucleotides (the basic components of DNA) are introduced into a living cell and, through a process known as homologous recombination, are exchanged with the defective portion of the genomic DNA. Other methods include use of RNA of the proper sequence to substitute for defective RNA formed from defective DNA. Although these methods ensure a properly functioning protein will be produced, in some cases it is advantageous to stop production of selected proteins in various disease states, such as in various viral infections, cardiovascular disease, or cancer.

RNA may be used to prevent production of specified proteins. For example, using antisense technology, single-stranded RNA or DNA (called the antisense strand) is administered to an individual and binds to a portion of the mRNA that will produce a specified protein. Once bound, it will physically block production of the protein, and the double-stranded molecule formed will then be degraded. Other methods to prevent protein synthesis utilizing RNA include RNA interference. In this method, double-stranded RNA is administered to an individual and it ultimately causes the target mRNA to be degraded, thereby preventing protein production, by a different mechanism than found in antisense technology. Vitravene (fomivirsen) is the first, and presently the only, antisense drug that the FDA has allowed to be marketed. It is used to treat a particular viral infection, cytomegalovirus retinitis, in individuals with AIDS. Many other antisense drugs are currently in various stages of development to treat a variety of other viral infections,
cardiovascular diseases, or cancers, including cancer of the colon, skin, lung, and prostate.

Perspective and Prospects

Artificial limbs have been in use for centuries, but no attempt was made to duplicate natural limbs except in the crudest sense. The use of microorganisms for the production of fermented beverages (such as beer, wine, and vinegar) and food (such as bread) goes back many centuries. Likewise, folk medicine made use of natural biochemicals to treat diseases for many centuries. These traditional processes, however, did not involve an understanding of what was occurring and may only be considered biotechnology by default. The knowledge needed for biotechnology required the development of several scientific disciplines, all of which only occurred after the 1950s, when scientifically understood and controlled processes were developed to produce biological products. It was not until the 1970s that recombinant DNA technology allowed significant advances in the understanding of many molecular and genetic processes.

The advancement of bionics and biotechnology after the 1950s was the result of advances made in related scientific fields during earlier decades, primarily after 1900. These developments included the discovery that enzymes were proteins and the theory of enzyme action; the discovery of the structure and function of vitamins; the discovery of the composition of nucleic acids; the discovery of the structure of carbohydrates; the development of a better understanding of the cellular infrastructure; work on natural and experimentally induced mutation; the study of hereditary metabolic errors; a better understanding of immunology, viral and bacterial diseases, tumors, and cell pathology; the realization that genes were found in the chromosomes; early studies concerning chromosome recombinations and the mechanisms of genetic expression; the ultraviolet analysis of DNA and RNA; the increased use of electron microscopy; the development of the technology involved in the large-scale production of penicillin; and the further development and integration of studies in genetics, biochemistry, and physiology.

The 1950s and 1960s saw important advances in the discovery of the structure of DNA, the breaking of the genetic code, the discovery of how gene actions were regulated, the structure of the gene and of numerous proteins, the discovery and study of numerous hereditary diseases, the development of medical procedures for organ transplants, the evolution of the branch of science known as molecular biology, and the continuing synthesis of discoveries and theories from a variety of scientific disciplines. The 1970s saw the development of technologies that further developed these areas of study, in particular recombinant DNA technology and monoclonal antibody technology. The future will see an increased refinement of these technologies and further developments resulting from the success of the Human Genome Project.

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