Opportunities in Biology (1989) / Chapter Skim
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10. Advances in Medicine, the Biochemical Process Industry, and Animal Agriculture
10. Advances in Medicine, the Biochemical Process Industry, and Animal Agriculture
Pages 323-364
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From page 323... ...
The rapidly expanding fields of cellular and molecular biology continue to generate possibilities for new pharmaceutical products and medical practices that will have major impacts on the prevention, diagnosis, and treatment of human disease. The application of biochemical and molecular understanding of cellular processes to product development in plant and animal agriculture lags behind that for medicine.
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From page 324... ...
The recognition Hat normal bodily function, cell-cell communication, and disease processes (such as inflammation, myocardial infarction, immune response, and allergy) are mediated by minute amounts of biologically active substances
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From page 325... ...
A fascinating discovery has arisen from the dietary manipulation of fatty acids in experimental animals. The depletion of arachidonic acid or its precursor from the diet produces essential fatty acid deficiency, which is life-saving in the autoimmune destruction of the kidney in mice genetically affected with glomerulonephritis (lupus)
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From page 326... ...
Thus, on the basis of a sound foundation of studies of arachidonic acid metabolism, specific therapeutic target areas can now be approached on a rational basis. Manipulation of the cyclooxygenase pathway could yield beneficial effects in immune response regulation and thrombosis, while manipulation of He lipoxygenase pathway, especially leukotriene synthesis, could provide a major new class of agents for the treatment of asthma, allergy, anaphylaxis, and inflammation (including myocardial infarction and renal disease)
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From page 327... ...
The atriopeptin-induced increase in glomerular filtration rate is striking, especially since it occurs at doses of peptide that decrease blood pressure and total renal blood flow. Autoradiography techniques have revealed high-affinity receptor sites for atriopeptin localized on the glomeruli and in the papillae of the kidney.
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From page 328... ...
Are Its Overt Manifestations Atherosclerosis, the disease process leading to the life-threatening events of heart attack and stroke, causes the progressive narrowing and eventual blocking of critical regions of the arterial bed. A major feature of the atherosclerotic lesion is the deposition of cholesterol in association with cell proliferation and connective tissue elaboration.
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From page 329... ...
. Each major class contains particles that are structurally and compositionally heterogeneous, are routed into different metabolic channels and may or may not give rise to potentially atherogenic particles.
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From page 330... ...
Research on the Structure and Synthesis of Apolipoproteins Will Lead to Insight into Cardiovascular Disease Apolipoproteins are determinants of major processes in lipoprotein assembly, secretion, extracellular processing, and catabolic removal, particularly via receptor-mediated pathways. Sequencing of many of the apolipoproteins has been accomplished, DNA clones for some of these have been obtained, and the mapping of apolipoprotein genes has proceeded.
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From page 331... ...
demonstrate extremes of abnormal lipoprotein distributions. For example, the investigation of the cellular biology of the LDL receptor has delineated a finely tuned system for regulating cellular cholesterol that affects plasma LDL levels.
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From page 332... ...
These studies have contributed valuable information on the major features of the macrophage receptors and their function. In addition, a role for the macrophage in converting smooth muscle cells to foam cells (lipid-laden cells)
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From page 333... ...
Platelets seem to release substances that stimulate the localized proliferation of smooth muscle. We now know that the proliferation of smooth muscle cells at sites where platelets interact can be partly due to the powerful growth factors produced by platelets, endothelial cells, macrophages, and the smooth muscle cells themselves.
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From page 334... ...
Inflammatory Joint Diseases and Seronegative Polyarthritis Remain Major Problems Although we know a great deal about its pathogenesis, we still do not understand the cause of the inflammatory joint disease rheumatoid arthritis. Specific antibodies called rheumatoid factors have been found in rheumatoid arthritis patients.
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From page 335... ...
should lead to a more precise genetic analysis and more extensive use of specific probes to define genetic susceptibility. Lyme Disease Might Be a Good Modelfor Understanding the Pathogenesis of Rheumatoid Arthritis Lyme disease was f~rst described in 1975 on the basis of observations of children with what was initially thought to be a form of juvenile polyarthritis.
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From page 336... ...
For these reasons, the major approach to this disabling disease is joint replacement. CANCER: CURRENT STATUS AND SOME NEW APPROACHES TO ITS CONTROL Cancer Has a Number of Causes Environmental and life-style risk factors such as the use of tobacco and alcohol, exposure to occupational carcinogens and pollutants, and diet are major causes of cancer.
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From page 337... ...
The second premise is that tumor cells proliferate more persistently than normal cells. This has given rise to the development of cancer chemotherapeutic agents, which take advantage of putative proliferative differences between normal and malignant cells.
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From page 338... ...
Further, these agents may produce alterations for which the cell can develop alternative mechanisms; selection of resistant clones of tumor cells seems to be the most prominent cause of failure, resulting in the development of cells resistant to the action of the chemotherapeutic agent. Mechanisms for this resistance include gene amplification and changes in membrane transport of chemotherapeutic drugs either into or out of the cell.
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From page 339... ...
Surgery removes the gross tumor and radiation therapy is applied to the larger region containing lower densities of cancer cells. Chemotherapy appears to be effective only against small volumes of tumor.
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From page 340... ...
A major goal for advancing the study of all of these viruses is to develop efficient and easy modes of infecting cells in culture. For the DNA viruses, this goal will be achieved either serendipitously or by developing more and easier methods of culturing epithelial cells than those available today.
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From page 341... ...
If a person who carries a gene associated with increased risk for a specific cancer could be identified, minimizing exposure to environmental hazards associated with induction of such cancers (for example, skin cancers attributable to ultraviolet light) or applying early detection methods to individuals at risk (for example, familial development of polyps and colon cancers)
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From page 342... ...
The general consensus is that tumor necrosis factor is part of a network of interactive signals for host immunological and antiinflammatory responses and in maintaining hematopoietic cell development in balance. Growth Factors.
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From page 343... ...
heterogeneity of tumors with respect to the amount of surface antigens on individual tumor cells to react with MAbs; (3) alterations in antigen on tumor cell surface causing the cells to be no longer recognized by the MAb; and (4)
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From page 344... ...
ADVANCES IN UNDERSTANDING HUMAN GENETIC DISORDERS Many Genetic Disorders Are Now Being Successfully Investigated Genetic mapping the localization of a gene or trait to a specific area on a chromosome-has created a great stir in the popular media and the biomedical literature alike during the 1980s. Diseases of interest include Huntington's disease, cystic fibrosis, polycystic kidney disease, neurofibromatosis, myotonic dystrophy, familial Alzheimer's disease, and Duchenne muscular dystrophy.
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From page 345... ...
Usually, in unraveling the pathophysiology and primary genetic defect in disorders inherited through classical Mendelian genetics, medical geneticists start with a phenotype that shows a "simple" pattern of inheritance; they identify a biochemical abnormality such as an abnormal metabolite in serum and urine; then they demonstrate the deficiency of an enzyme that could plausibly account for the abnormal metabolize; they clone the normal gene for the enzyme in question; and perhaps ultimately they determine the change in the gene in patients with the disorder. In many disorders, however, no clue exists to the nature of the defective protein gene product.
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From page 346... ...
Demonstrating that the normal gene cloned by these methods is indeed the one that is mutant in the given disorder can be accomplished through several approaches. Finding the mutation in a protein gene that has been linked to the disease by additional lines of evidence is a good indication that the mutation is responsible for the disease.
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From page 347... ...
indicates that somatic cell gene therapy of some
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From page 348... ...
In some disorders in which an abnormal protein leads to abnormality for example, sickle cell anemia and amyloid polyneuropathy merely introducing a normal gene may not solve the problem. Ablation of the abnormal gene may be necessary.
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From page 349... ...
This limits its potentially toxic effects on uninfected cells. Vaccines The Development of an HIV Vaccine to Prevent Acquired Immune Deficiency Syndrome Is Progressing Slowly A new disease of humans, acquired immune deficiency syndrome (AIDS)
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From page 350... ...
Such "anti-antibodies" have a configuration that resembles the immunogenic protein. Anti-idiotypes prime or actually stimulate an effective immune response.
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From page 351... ...
Selected drugs that affect early events include heparin and other anionic polyelectrolytes, which prevent attachment; oligopeptides, which by mimicking part of the fusion polypeptide of paramyxoviruses inhibit fusion; and amantadine and rimatadine, which inhibit early steps in the growth of type A influenza. Drugs that affect the synthesis of
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From page 352... ...
It was not until the mid-1940s, however, that a true collaboration between the biological scientist and the process engineer began to develop. It has recently become apparent that biological discovery provides the driving force behind process development: The new discoveries in biology during the past decade have become the enabling technologies that underlie a modem and rapidly growing biochemical process industry.
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From page 353... ...
However, for discoveries to be translated into products the techniques for developing biochemical processes must be available and manpower must be adequate. To fully appreciate and understand the problems and opportunities associated with industrial biotechnology, it is essential to examine the barriers inherent in product development.
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From page 354... ...
This reactor may be a fermenter for growing microorganisms or a device for propagation of animal cells; in either case, the cells may have been genetically engineered to overproduce the desired producL Once formed, the product must be separated, concentrated, and purified to its active form and formulated to stabilize, and perhaps enhance, its activity for eventual use as a drug. A process for manufacturing therapeutic proteins derived from recombinant microorganisms is expensive and complex, not only because of the multiple unit operations that must be carried out to recover highly pure materials, but also because the final product must be made in its native form that is, with a single three-dimensional structure.
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From page 355... ...
by cells, the function of which we need to better understand; we also need to improve the techniques for characterizing, modifying, and recovering properly glycosylated proteins. Additionally, a substantial number of proteins of interest form insoluble aggregates or "inclusion bodies" inside genetically engineered cells, and we need to better understand procedures for recovering these proteins.
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From page 356... ...
Thus, the use of well-defined, low-protein media.areatly enhances efficient product recovery. c ~_ ~ Modern Biology Coupled to the Biochemical Processing Industry Has Enormous Potential Human Growth Hormone.
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From page 357... ...
More than a score of companies are currently involved in the research and development of tissue plasminogen activator. The story differs considerably from that for human growth hormone production.
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From page 358... ...
Industrial Growth in Biotechnology Is Predicted, but International Competition Will Be Great Over the past 5 years, biotechnology, defined as the application of biological organisms, systems, and processes to the manufacturing and service industries, has developed dramatically, and commercial products have been made. Although the number of products that have entered the market at this time is limited (for example, insulin, human growth hormone, interferons, tissue plasminogen activator, and hepatitis B vaccine)
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From page 359... ...
ADVANCES IN ANIMAL AGRICULTURE Challenges Lie Ahead to Increase the Efficiency and Productivity of Domestic Animals Under Widely Disparate Environmental, Economic, awl Political Constraints Of the thousands of animal species that might have been domesticated, human beings have utilized only a handful. These have been selected over the last 10 millennia to occupy increasingly narrow ecological niches.
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From page 360... ...
Since growth hormone does more than produce somatomedins, it is likely that this approach or the use of releasing factors will be the method of choice for the immediate future. However, the use of somatomedins and epidermal growth factors has been proposed for wound healing in valuable animals.
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From page 361... ...
In addition, the management systems in place for most domestic animals stress the reproductive process. For instance, increasing mink yield in cattle through genetic selection has had detrimental effects on reproductive performance because of the large metabolic demands to increase mink production.
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From page 362... ...
Although several potential mammary growth factors have been identified, the specific roles these various factors play in regulating tissue growth are not well understood. If specific mammary growth factors could be identified and put to use, it would benefit not only the dairy industry, but also other animal industries as well, since milk production is a major [imitating factor on the growth rate of neonatal swine and beef cattle.
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From page 363... ...
A similar approach has been successful in preventing the attachment to mammary epithelial cells of certain bacteria that cause mastitis. Production of Feedstocks Some Feed Additives, Such As Amino Acids and Vitamins, May Be Efficiently Produced by Recombinant Techniques The two major amino acids now used as feed additives are methionine and ~lysine.
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From page 364... ...
For example, adaptation to thermal stress is associated with a reduction in circulating somatotropin concentrations. Growth rates and mink yields of cattle in these regions might be enhanced markedly with exogenous supplementation of somatotropin or insertion of extra copies of the growth hormone gene.
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