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117-496: A recombinant form of HGH called somatropin ( INN ) is used as a prescription drug to treat children's growth disorders and adult growth hormone deficiency . In the United States, it is only available legally from pharmacies by prescription from a licensed health care provider. In recent years in the United States, some health care providers are prescribing growth hormone in the elderly to increase vitality . While legal,

234-462: A cloning vector , a DNA molecule that replicates within a living cell. Vectors are generally derived from plasmids or viruses , and represent relatively small segments of DNA that contain necessary genetic signals for replication, as well as additional elements for convenience in inserting foreign DNA, identifying cells that contain recombinant DNA, and, where appropriate, expressing the foreign DNA. The choice of vector for molecular cloning depends on

351-440: A plane , e.g. graphene ; or three-dimensionally e.g. diamond , quartz , sodium chloride . The theme of repeated unit-cellular-structure also holds for most metals which are condensed phases with metallic bonding . Thus solid metals are not made of molecules. In glasses , which are solids that exist in a vitreous disordered state, the atoms are held together by chemical bonds with no presence of any definable molecule, nor any of

468-512: A 15-year-old female with well-documented hypopituitarism secondary to a craniopharyngioma; a 53-year-old female with carcinoma of the breast and widespread skeletal metastases; a 68-year-old female with advanced postmenopausal osteoporosis; and a healthy 24-year-old medical student without any clinical or laboratory evidence of systemic disease. In 1985, unusual cases of Creutzfeldt–Jakob disease were found in individuals that had received cadaver-derived HGH ten to fifteen years previously. Based on

585-419: A 22 kDa glycosylated variant of 23 kDa identified in the pituitary gland. Furthermore, these variants circulate partially bound to a protein ( growth hormone-binding protein , GHBP), which is the truncated part of the growth hormone receptor , and an acid-labile subunit (ALS). Secretion of growth hormone (GH) in the pituitary is regulated by the neurosecretory nuclei of the hypothalamus . These cells release

702-402: A GH antagonist such as pegvisomant may be employed to shrink the tumor or block function. Other drugs like octreotide (somatostatin agonist) and bromocriptine ( dopamine agonist ) can be used to block GH secretion because both somatostatin and dopamine negatively inhibit GHRH-mediated GH release from the anterior pituitary. The effects of growth hormone (GH) deficiency vary depending on

819-524: A U.S. patent on recombinant DNA on November 4, 1974, listing the inventors as Herbert W. Boyer (professor at the University of California, San Francisco ) and Stanley N. Cohen (professor at Stanford University ); this patent, U.S. 4,237,224A, was awarded on December 2, 1980. The first licensed drug generated using recombinant DNA technology was human insulin, developed by Genentech and licensed by Eli Lilly and Company . Scientists associated with

936-569: A certain number of these atoms united by attraction to form a single molecule . In coordination with these concepts, in 1833 the French chemist Marc Antoine Auguste Gaudin presented a clear account of Avogadro's hypothesis, regarding atomic weights, by making use of "volume diagrams", which clearly show both semi-correct molecular geometries, such as a linear water molecule, and correct molecular formulas, such as H 2 O: In 1917, an unknown American undergraduate chemical engineer named Linus Pauling

1053-399: A dimension of a few angstroms (Å) to several dozen Å, or around one billionth of a meter. Single molecules cannot usually be observed by light (as noted above), but small molecules and even the outlines of individual atoms may be traced in some circumstances by use of an atomic force microscope . Some of the largest molecules are macromolecules or supermolecules . The smallest molecule

1170-435: A graphical type of formula called a structural formula may be needed. Structural formulas may in turn be represented with a one-dimensional chemical name, but such chemical nomenclature requires many words and terms which are not part of chemical formulas. Molecules have fixed equilibrium geometries—bond lengths and angles— about which they continuously oscillate through vibrational and rotational motions. A pure substance

1287-622: A group of homologous hormones with growth-promoting and lactogenic activity. The major isoform of the human growth hormone is a protein of 191 amino acids and a molecular weight of 22,124 daltons . The structure includes four helices necessary for functional interaction with the GH receptor. It appears that, in structure, GH is evolutionarily homologous to prolactin and chorionic somatomammotropin. Despite marked structural similarities between growth hormone from different species , only human and Old World monkey growth hormones have significant effects on

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1404-867: A month has been found to be as safe and effective as daily growth hormone injections. GH can be used to treat conditions that produce short stature but are not related to deficiencies in GH. However, results are not as dramatic when compared to short stature that is solely attributable to deficiency of GH. Examples of other causes of shortness often treated with GH are Turner syndrome , Growth failure secondary to chronic kidney disease in children, Prader–Willi syndrome , intrauterine growth restriction , and severe idiopathic short stature . Higher ("pharmacologic") doses are required to produce significant acceleration of growth in these conditions, producing blood levels well above normal ("physiologic"). One version of rHGH has also been FDA approved for maintaining muscle mass in wasting due to AIDS . Off-label prescription of HGH

1521-522: A multiple-step diagnostic process, usually culminating in GH stimulation tests to see if the patient's pituitary gland will release a pulse of GH when provoked by various stimuli. Several studies, primarily involving patients with GH deficiency , have suggested a crucial role of GH in both mental and emotional well-being and maintaining a high energy level. Adults with GH deficiency often have higher rates of depression than those without. While GH replacement therapy has been proposed to treat depression as

1638-447: A non-pathogenic strain (K-12) of E. coli bacteria for large-scale laboratory production of the enzyme. This microbiologically produced recombinant enzyme, identical structurally to the calf derived enzyme, costs less and is produced in abundant quantities. Today about 60% of U.S. hard cheese is made with genetically engineered chymosin. In 1990, FDA granted chymosin " generally recognized as safe " (GRAS) status based on data showing that

1755-711: A professor in the Biochemistry Department at Stanford and an author on one of the first papers was awarded the Nobel Prize in Chemistry for his work on nucleic acids "with particular regard to recombinant DNA". Werner Arber , Hamilton Smith , and Daniel Nathans shared the 1978 Nobel Prize in Physiology or Medicine for the discovery of restriction endonucleases which enhanced the techniques of rDNA technology. Stanford University applied for

1872-426: A rare form of type 2 diabetes , and reduced sexual function. GH-secreting tumors are typically recognized in the fifth decade of life. It is extremely rare for such a tumor to occur in childhood, but, when it does, the excessive GH can cause excessive growth, traditionally referred to as pituitary gigantism . Surgical removal is the usual treatment for GH-producing tumors. In some circumstances, focused radiation or

1989-470: A rare growth defect in children and a handful of uncommon conditions like short bowel syndrome or Prader-Willi syndrome, a congenital disease that causes reduced muscle tone and a lack of hormones in sex glands." At the same time, anti-aging clinics where doctors prescribe, administer, and sell HGH to people are big business. In a 2012 article in Vanity Fair , when asked how HGH prescriptions far exceed

2106-401: A regular arrangement of molecules (as in a crystal). Microwave spectroscopy commonly measures changes in the rotation of molecules, and can be used to identify molecules in outer space. Infrared spectroscopy measures the vibration of molecules, including stretching, bending or twisting motions. It is commonly used to identify the kinds of bonds or functional groups in molecules. Changes in

2223-452: A result of GH deficiency, the long-term effects of such therapy are unknown. GH has also been studied in the context of cognitive function , including learning and memory. GH in humans appears to improve cognitive function and may be useful in the treatment of patients with cognitive impairment that is a result of GH deficiency. GH is used as replacement therapy in adults with GH deficiency of either childhood-onset or adult-onset (usually as

2340-526: A result of an acquired pituitary tumor). In these patients, benefits have variably included reduced fat mass, increased lean mass, increased bone density, improved lipid profile, reduced cardiovascular risk factors, and improved psychosocial well-being. Long acting growth hormone (LAGH) analogues are now available for treating growth hormone deficiency both in children and adults. These are once weekly injections as compared to conventional growth hormone which has to be taken as daily injections. LAGH injection 4 times

2457-401: A significant enhancement of nitrogen storage ... (and) there was a retention of potassium, phosphorus, calcium, and sodium. ... There was a gain in body weight during both periods. ... There was a significant increase in urinary excretion of aldosterone during both periods of administration of growth hormone. This was most marked with the human growth hormone. ... Impairment of

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2574-435: Is a bacterium that naturally produces a protein ( Bt toxin ) with insecticidal properties. The bacterium has been applied to crops as an insect-control strategy for many years, and this practice has been widely adopted in agriculture and gardening. Recently, plants have been developed that express a recombinant form of the bacterial protein, which may effectively control some insect predators. Environmental issues associated with

2691-402: Is a chemical bond that involves the sharing of electron pairs between atoms. These electron pairs are termed shared pairs or bonding pairs , and the stable balance of attractive and repulsive forces between atoms, when they share electrons, is termed covalent bonding . Ionic bonding is a type of chemical bond that involves the electrostatic attraction between oppositely charged ions, and

2808-497: Is a drug. Also, under United States law, products sold as dietary supplements cannot have claims that the supplement treats or prevents any disease or condition, and the advertising material must contain a statement that the health claims are not approved by the FDA. The FTC and the FDA do enforce the law when they become aware of violations. In the United States, it is legal to give a bovine GH to dairy cows to increase milk production, and

2925-477: Is a group of two or more atoms that are held together by attractive forces known as chemical bonds ; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics , organic chemistry , and biochemistry , the distinction from ions is dropped and molecule is often used when referring to polyatomic ions . A molecule may be homonuclear , that is, it consists of atoms of one chemical element , e.g. two atoms in

3042-455: Is a very simple type of chemical formula. It is the simplest integer ratio of the chemical elements that constitute it. For example, water is always composed of a 2:1 ratio of hydrogen to oxygen atoms, and ethanol (ethyl alcohol) is always composed of carbon, hydrogen, and oxygen in a 2:6:1 ratio. However, this does not determine the kind of molecule uniquely – dimethyl ether has the same ratios as ethanol, for instance. Molecules with

3159-452: Is abbreviated hGH . The main growth hormone produced by recombinant DNA technology has the approved generic name ( INN ) somatropin and the brand name Humatrope and is properly abbreviated rhGH in the scientific literature. Since its introduction in 1992, Humatrope has been a banned sports doping agent and in this context is referred to as HGH. The term growth hormone has been incorrectly applied to refer to anabolic sex hormones in

3276-505: Is after chronic use patients don't develop an immune defence against it the way animal sourced insulin stimulates the human immune system. Administered to patients whose pituitary glands generate insufficient quantities to support normal growth and development. Before recombinant HGH became available, HGH for therapeutic use was obtained from pituitary glands of cadavers. This unsafe practice led to some patients developing Creutzfeldt–Jakob disease . Recombinant HGH eliminated this problem, and

3393-489: Is by inappropriate activation of previously unexpressed host cell genes. This can happen, for example, when a recombinant DNA fragment containing an active promoter becomes located next to a previously silent host cell gene, or when a host cell gene that functions to restrain gene expression undergoes insertional inactivation by recombinant DNA. Recombinant DNA is widely used in biotechnology , medicine and research. Today, recombinant proteins and other products that result from

3510-435: Is composed of molecules with the same average geometrical structure. The chemical formula and the structure of a molecule are the two important factors that determine its properties, particularly its reactivity . Isomers share a chemical formula but normally have very different properties because of their different structures. Stereoisomers , a particular type of isomer, may have very similar physico-chemical properties and at

3627-499: Is controversial and may be illegal. Claims for GH as an anti-aging treatment date back to 1990 when the New England Journal of Medicine published a study wherein GH was used to treat 12 men over 60. At the conclusion of the study, all the men showed statistically significant increases in lean body mass and bone mineral density, while the control group did not. The authors of the study noted that these improvements were

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3744-483: Is derived from French molécule (1678), from Neo-Latin molecula , diminutive of Latin moles "mass, barrier". The word, which until the late 18th century was used only in Latin form, became popular after being used in works of philosophy by Descartes . The definition of the molecule has evolved as knowledge of the structure of molecules has increased. Earlier definitions were less precise, defining molecules as

3861-486: Is essential for the understanding of the chemical bond. The simplest of molecules is the hydrogen molecule-ion , H 2 , and the simplest of all the chemical bonds is the one-electron bond . H 2 is composed of two positively charged protons and one negatively charged electron , which means that the Schrödinger equation for the system can be solved more easily due to the lack of electron–electron repulsion. With

3978-752: Is in basic research, in which the technology is important to most current work in the biological and biomedical sciences. Recombinant DNA is used to identify, map and sequence genes, and to determine their function. rDNA probes are employed in analyzing gene expression within individual cells, and throughout the tissues of whole organisms. Recombinant proteins are widely used as reagents in laboratory experiments and to generate antibody probes for examining protein synthesis within cells and organisms. Many additional practical applications of recombinant DNA are found in industry, food production, human and veterinary medicine, agriculture, and bioengineering. Some specific examples are identified below. Found in rennet , chymosin

4095-464: Is legal to use GH in raising cows for beef; see article on Bovine somatotropin , cattle feeding , dairy farming and the beef hormone controversy . The use of GH in poultry farming is illegal in the United States. Similarly, no chicken meat for sale in Australia is administered hormones. Several companies have attempted to have a version of GH for use in pigs (porcine somatotropin) approved by

4212-410: Is now used therapeutically. It has also been misused as a performance-enhancing drug by athletes and others. It is the recombinant form of factor VIII , a blood-clotting protein that is administered to patients with the bleeding disorder hemophilia , who are unable to produce factor VIII in quantities sufficient to support normal blood coagulation. Before the development of recombinant factor VIII,

4329-416: Is possible because DNA molecules from all organisms share the same chemical structure, differing only in the nucleotide sequence. Recombinant DNA molecules are sometimes called chimeric DNA because they can be made of material from two different species like the mythical chimera . rDNA technology uses palindromic sequences and leads to the production of sticky and blunt ends . The DNA sequences used in

4446-551: Is produced in yeast cells. The development of the recombinant subunit vaccine was an important and necessary development because hepatitis B virus, unlike other common viruses such as polio virus , cannot be grown in vitro . Recombinant antibodies (rAbs) are produced in vitro by the means of expression systems based on mammalian cells. Their monospecific binding to a specific epitope makes rAbs eligible not only for research purposes, but also as therapy options against certain cancer types, infections and autoimmune diseases. Each of

4563-415: Is rare in adults, with the most common cause being a pituitary adenoma . Other adult causes include a continuation of a childhood problem, other structural lesions or trauma , and very rarely idiopathic GHD. Adults with GHD "tend to have a relative increase in fat mass and a relative decrease in muscle mass and, in many instances, decreased energy and quality of life". Diagnosis of GH deficiency involves

4680-556: Is the diatomic hydrogen (H 2 ), with a bond length of 0.74 Å. Effective molecular radius is the size a molecule displays in solution. The table of permselectivity for different substances contains examples. The chemical formula for a molecule uses one line of chemical element symbols, numbers, and sometimes also other symbols, such as parentheses, dashes, brackets, and plus (+) and minus (−) signs. These are limited to one typographic line of symbols, which may include subscripts and superscripts. A compound's empirical formula

4797-414: Is the enzyme responsible for hydrolysis of κ - casein to produce para- κ -casein and glycomacropeptide , which is the first step in formation of cheese , and subsequently curd , and whey . It was the first genetically engineered food additive used commercially. Traditionally, processors obtained chymosin from rennet, a preparation derived from the fourth stomach of milk-fed calves. Scientists engineered

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4914-617: Is the primary interaction occurring in ionic compounds . The ions are atoms that have lost one or more electrons (termed cations ) and atoms that have gained one or more electrons (termed anions ). This transfer of electrons is termed electrovalence in contrast to covalence . In the simplest case, the cation is a metal atom and the anion is a nonmetal atom, but these ions can be of a more complicated nature, e.g. molecular ions like NH 4 or SO 4 . At normal temperatures and pressures, ionic bonding mostly creates solids (or occasionally liquids) without separate identifiable molecules, but

5031-509: The 2004 Olympic Games in Athens, Greece , targeted primarily HGH. Use of the drug for performance enhancement is not currently approved by the FDA . GH has been studied for use in raising livestock more efficiently in industrial agriculture and several efforts have been made to obtain governmental approval to use GH in livestock production. These uses have been controversial. In the United States,

5148-534: The Avogadro constant using three different methods, all involving liquid phase systems. First, he used a gamboge soap-like emulsion, second by doing experimental work on Brownian motion , and third by confirming Einstein's theory of particle rotation in the liquid phase. In 1927, the physicists Fritz London and Walter Heitler applied the new quantum mechanics to the deal with the saturable, nondynamic forces of attraction and repulsion, i.e., exchange forces, of

5265-496: The anterior pituitary gland then synthesize and secrete GH in a pulsatile manner, in response to these stimuli by the hypothalamus. The largest and most predictable of these GH peaks occurs about an hour after onset of sleep with plasma levels of 13 to 72 ng/mL. Maximal secretion of GH may occur within minutes of the onset of slow-wave (SW) sleep (stage III or IV). Otherwise there is wide variation between days and individuals. Nearly fifty percent of GH secretion occurs during

5382-684: The oxygen molecule (O 2 ); or it may be heteronuclear , a chemical compound composed of more than one element, e.g. water (two hydrogen atoms and one oxygen atom; H 2 O). In the kinetic theory of gases , the term molecule is often used for any gaseous particle regardless of its composition. This relaxes the requirement that a molecule contains two or more atoms, since the noble gases are individual atoms. Atoms and complexes connected by non-covalent interactions , such as hydrogen bonds or ionic bonds , are typically not considered single molecules. Concepts similar to molecules have been discussed since ancient times, but modern investigation into

5499-476: The Chemical Bond" in which he used quantum mechanics to calculate properties and structures of molecules, such as angles between bonds and rotation about bonds. On these concepts, Pauling developed hybridization theory to account for bonds in molecules such as CH 4 , in which four sp³ hybridised orbitals are overlapped by hydrogen 's 1s orbital, yielding four sigma (σ) bonds . The four bonds are of

5616-642: The European beef hormone controversy , which initially restricts the use of estradiol , progesterone , testosterone , zeranol , melengestrol acetate and trenbolone acetate . Genes for human growth hormone, known as growth hormone 1 (somatotropin; pituitary growth hormone) and growth hormone 2 (placental growth hormone; growth hormone variant), are localized in the q22-24 region of chromosome 17 and are closely related to human chorionic somatomammotropin (also known as placental lactogen ) genes. GH, human chorionic somatomammotropin, and prolactin belong to

5733-421: The FDA but all applications have been withdrawn. Genentech pioneered the use of recombinant human growth hormone for human therapy, which was approved by the FDA in 1985. Prior to its production by recombinant DNA technology, growth hormone used to treat deficiencies was extracted from the pituitary glands of cadavers . Attempts to create a wholly synthetic HGH failed. Limited supplies of HGH resulted in

5850-454: The RT-PCR test was made possible by the molecular cloning and sequence analysis of HIV genomes. HIV testing page from US Centers for Disease Control (CDC) Golden rice is a recombinant variety of rice that has been engineered to express the enzymes responsible for β-carotene biosynthesis. This variety of rice holds substantial promise for reducing the incidence of vitamin A deficiency in

5967-500: The U.S. Food and Drug Administration (FDA) approved a version of rHGH called Omnitrope (Sandoz). A sustained-release form of growth hormone, Nutropin Depot (Genentech and Alkermes) was approved by the FDA in 1999, allowing for fewer injections (every 2 or 4 weeks instead of daily); however, the product was discontinued by Genentech/Alkermes in 2004 for financial reasons (Nutropin Depot required significantly more resources to produce than

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6084-404: The advertising text, with medical-sounding names described as "HGH Releasers". Typical ingredients include amino acids, minerals, vitamins, and/or herbal extracts, the combination of which are described as causing the body to make more GH with corresponding beneficial effects. In the United States, because these products are marketed as dietary supplements, it is illegal for them to contain GH, which

6201-557: The age at which they occur. Alterations in somatomedin can result in growth hormone deficiency with two known mechanisms; failure of tissues to respond to somatomedin , or failure of the liver to produce somatomedin. Major manifestations of GH deficiency in children are growth failure , the development of a short stature , and delayed sexual maturity. In adults, somatomedin alteration contributes to increased osteoclast activity, resulting in weaker bones that are more prone to pathologic fracture and osteoporosis . However, deficiency

6318-441: The arrangements of electrons yield absorption or emission lines in ultraviolet, visible or near infrared light, and result in colour. Nuclear resonance spectroscopy measures the environment of particular nuclei in the molecule, and can be used to characterise the numbers of atoms in different positions in a molecule. The study of molecules by molecular physics and theoretical chemistry is largely based on quantum mechanics and

6435-442: The articles on genetically modified organisms and genetically modified food controversies . Furthermore, there are concerns about the by-products in biopharmaceutical production, where recombinant DNA result in specific protein products. The major by-product, termed host cell protein , comes from the host expression system and poses a threat to the patient's health and the overall environment. Molecule A molecule

6552-536: The assumption that infectious prions causing the disease were transferred along with the cadaver-derived HGH, cadaver-derived HGH was removed from the market. In 1985, biosynthetic human growth hormone replaced pituitary-derived human growth hormone for therapeutic use in the U.S. and elsewhere. As of 2005, recombinant growth hormones available in the United States (and their manufacturers) included Nutropin ( Genentech ), Humatrope ( Lilly ), Genotropin ( Pfizer ), Norditropin ( Novo ), and Saizen ( Merck Serono ). In 2006,

6669-682: The authors of a commentary article published in the Journal of the American Medical Association in 2005, as meaning that prescribing HGH off-label may be considered illegal. And some articles in the popular press, such as those criticizing the pharmaceutical industry for marketing drugs for off-label use (with concern of ethics violations) have made strong statements about whether doctors can prescribe HGH off-label: "Unlike other prescription drugs, HGH may be prescribed only for specific uses. U.S. sales are limited by law to treat

6786-425: The body store more water in the muscles rather than increase muscle growth. This would explain the increase in lean body mass. GH has also been used experimentally to treat multiple sclerosis , to enhance weight loss in obesity , as well as in fibromyalgia , heart failure , Crohn's disease and ulcerative colitis , and burns. GH has also been used experimentally in patients with short bowel syndrome to lessen

6903-457: The body: GH has a short biological half-life of about 10 to 20 minutes. The most common disease of GH excess is a pituitary tumor composed of somatotroph cells of the anterior pituitary. These somatotroph adenomas are benign and grow slowly, gradually producing more and more GH. For years, the principal clinical problems are those of GH excess. Eventually, the adenoma may become large enough to cause headaches, impair vision by pressure on

7020-586: The choice of host organism, the size of the DNA to be cloned, and whether and how the foreign DNA is to be expressed. The DNA segments can be combined by using a variety of methods, such as restriction enzyme/ligase cloning or Gibson assembly . In standard cloning protocols, the cloning of any DNA fragment essentially involves seven steps: (1) Choice of host organism and cloning vector, (2) Preparation of vector DNA, (3) Preparation of DNA to be cloned, (4) Creation of recombinant DNA, (5) Introduction of recombinant DNA into

7137-495: The construction of recombinant DNA molecules can originate from any species . For example, plant DNA can be joined to bacterial DNA, or human DNA can be joined with fungal DNA. In addition, DNA sequences that do not occur anywhere in nature can be created by the chemical synthesis of DNA and incorporated into recombinant DNA molecules. Using recombinant DNA technology and synthetic DNA, any DNA sequence can be created and introduced into living organisms. Proteins that can result from

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7254-484: The development of fast digital computers, approximate solutions for more complicated molecules became possible and are one of the main aspects of computational chemistry . When trying to define rigorously whether an arrangement of atoms is sufficiently stable to be considered a molecule, IUPAC suggests that it "must correspond to a depression on the potential energy surface that is deep enough to confine at least one vibrational state". This definition does not depend on

7371-582: The efficacy and safety of this use for HGH has not been tested in a clinical trial. Many of the functions of HGH remain unknown. In its role as an anabolic agent, HGH has been used by competitors in sports since at least 1982 and has been banned by the IOC and NCAA . Traditional urine analysis does not detect doping with HGH, so the ban was not enforced until the early 2000s, when blood tests that could distinguish between natural and artificial HGH were starting to be developed. Blood tests conducted by WADA at

7488-690: The enzyme was safe. Recombinant human insulin has almost completely replaced insulin obtained from animal sources (e.g. pigs and cattle) for the treatment of type 1 diabetes . A variety of different recombinant insulin preparations are in widespread use. Recombinant insulin is synthesized by inserting the human insulin gene into E. coli , or yeast (Saccharomyces cerevisiae) which then produces insulin for human use. Insulin produced by E. coli requires further post translational modifications (e.g. glycosylation) whereas yeasts are able to perform these modifications themselves by virtue of being more complex host organisms. The advantage of recombinant human insulin

7605-402: The experimentalist. There are two fundamental differences between the methods. One is that molecular cloning involves replication of the DNA within a living cell, while PCR replicates DNA in the test tube, free of living cells. The other difference is that cloning involves cutting and pasting DNA sequences, while PCR amplifies by copying an existing sequence. Formation of recombinant DNA requires

7722-440: The expression of recombinant DNA within living cells are termed recombinant proteins . When recombinant DNA encoding a protein is introduced into a host organism, the recombinant protein is not necessarily produced. Expression of foreign proteins requires the use of specialized expression vectors and often necessitates significant restructuring by foreign coding sequences. Recombinant DNA differs from genetic recombination in that

7839-417: The former results from artificial methods while the latter is a normal biological process that results in the remixing of existing DNA sequences in essentially all organisms. Molecular cloning is the laboratory process used to produce recombinant DNA. It is one of two most widely used methods, along with polymerase chain reaction (PCR), used to direct the replication of any specific DNA sequence chosen by

7956-474: The glucose tolerance curve was evident after 10 days of administration of the human growth hormone. No change in glucose tolerance was demonstrable on the fifth day of administration of monkey growth hormone." The other study, published in 1958, was conducted on six people: the same subject as the Science paper; an 18-year-old male with statural and sexual retardation and a skeletal age of between 13 and 14 years;

8073-464: The heavenly bodies. The viewpoint of Leucippus and Empedocles, along with the aether, was accepted by Aristotle and passed to medieval and renaissance Europe. In a more concrete manner, however, the concept of aggregates or units of bonded atoms, i.e. "molecules", traces its origins to Robert Boyle 's 1661 hypothesis, in his famous treatise The Sceptical Chymist , that matter is composed of clusters of particles and that chemical change results from

8190-582: The host organism induced by the recombinant gene product, especially if it is over-expressed or expressed within inappropriate cells or tissues. In some cases, recombinant DNA can have deleterious effects even if it is not expressed. One mechanism by which this happens is insertional inactivation , in which the rDNA becomes inserted into a host cell's gene. In some cases, researchers use this phenomenon to " knock out " genes to determine their biological function and importance. Another mechanism by which rDNA insertion into chromosomal DNA can affect gene expression

8307-486: The host organism, (6) Selection of organisms containing recombinant DNA, and (7) Screening for clones with desired DNA inserts and biological properties. These steps are described in some detail in a related article ( molecular cloning ). DNA expression requires the transfection of suitable host cells. Typically, either bacterial, yeast, insect, or mammalian cells (such as Human Embryonic Kidney cells or CHO cells ) are used as host cells. Following transplantation into

8424-430: The host organism, the foreign DNA contained within the recombinant DNA construct may or may not be expressed . That is, the DNA may simply be replicated without expression, or it may be transcribed and translated and a recombinant protein is produced. Generally speaking, expression of a foreign gene requires restructuring the gene to include sequences that are required for producing an mRNA molecule that can be used by

8541-432: The host's translational apparatus (e.g. promoter , translational initiation signal , and transcriptional terminator ). Specific changes to the host organism may be made to improve expression of the ectopic gene. In addition, changes may be needed to the coding sequences as well, to optimize translation, make the protein soluble, direct the recombinant protein to the proper cellular or extracellular location, and stabilize

8658-462: The human growth hormone receptor . Several molecular isoforms of GH exist in the pituitary gland and are released to blood. In particular, a variant of approximately 20 kDa originated by an alternative splicing is present in a rather constant 1:9 ratio, while recently an additional variant of ~ 23-24 kDa has also been reported in post-exercise states at higher proportions. This variant has not been identified, but it has been suggested to coincide with

8775-589: The hydrogen molecule. Their valence bond treatment of this problem, in their joint paper, was a landmark in that it brought chemistry under quantum mechanics. Their work was an influence on Pauling, who had just received his doctorate and visited Heitler and London in Zürich on a Guggenheim Fellowship . Subsequently, in 1931, building on the work of Heitler and London and on theories found in Lewis' famous article, Pauling published his ground-breaking article "The Nature of

8892-400: The initial development of recombinant DNA methods recognized that the potential existed for organisms containing recombinant DNA to have undesirable or dangerous properties. At the 1975 Asilomar Conference on Recombinant DNA , these concerns were discussed and a voluntary moratorium on recombinant DNA research was initiated for experiments that were considered particularly risky. This moratorium

9009-735: The laws governing their structure and properties. In practice, however, this distinction is vague. In molecular sciences, a molecule consists of a stable system ( bound state ) composed of two or more atoms. Polyatomic ions may sometimes be usefully thought of as electrically charged molecules. The term unstable molecule is used for very reactive species, i.e., short-lived assemblies ( resonances ) of electrons and nuclei , such as radicals , molecular ions , Rydberg molecules , transition states , van der Waals complexes , or systems of colliding atoms as in Bose–Einstein condensate . Molecules as components of matter are common. They also make up most of

9126-404: The mass of a neutral carbon-12 ( C isotope ) atom. For network solids , the term formula unit is used in stoichiometric calculations. For molecules with a complicated 3-dimensional structure, especially involving atoms bonded to four different substituents, a simple molecular formula or even semi-structural chemical formula may not be enough to completely specify the molecule. In this case,

9243-452: The minerals that make up the substance of the Earth, sand, clay, pebbles, rocks, boulders, bedrock , the molten interior , and the core of the Earth . All of these contain many chemical bonds, but are not made of identifiable molecules. No typical molecule can be defined for salts nor for covalent crystals , although these are often composed of repeating unit cells that extend either in

9360-552: The nature of molecules and their bonds began in the 17th century. Refined over time by scientists such as Robert Boyle , Amedeo Avogadro , Jean Perrin , and Linus Pauling , the study of molecules is today known as molecular physics or molecular chemistry. According to Merriam-Webster and the Online Etymology Dictionary , the word "molecule" derives from the Latin " moles " or small unit of mass. The word

9477-440: The nature of the interaction between the atoms, but only on the strength of the interaction. In fact, it includes weakly bound species that would not traditionally be considered molecules, such as the helium dimer , He 2 , which has one vibrational bound state and is so loosely bound that it is only likely to be observed at very low temperatures. Whether or not an arrangement of atoms is sufficiently stable to be considered

9594-444: The number of adult patients estimated to have HGH-deficiency, Dragos Roman, who leads a team at the FDA that reviews drugs in endocrinology, said "The F.D.A. doesn't regulate off-label uses of H.G.H. Sometimes it's used appropriately. Sometimes it's not." Injection site reactions are common. More rarely, patients can experience joint swelling, joint pain, carpal tunnel syndrome , and an increased risk of diabetes . In some cases,

9711-517: The oceans and atmosphere. Most organic substances are molecules. The substances of life are molecules, e.g. proteins, the amino acids of which they are composed, the nucleic acids (DNA and RNA), sugars, carbohydrates, fats, and vitamins. The nutrient minerals are generally ionic compounds, thus they are not molecules, e.g. iron sulfate. However, the majority of familiar solid substances on Earth are made partly or completely of crystals or ionic compounds, which are not made of molecules. These include all of

9828-450: The only FDA-approved use of GH for livestock is the use of a cow-specific form of GH called bovine somatotropin for increasing milk production in dairy cows. Retailers are permitted to label containers of milk as produced with or without bovine somatotropin. The names somatotropin ( STH ) or somatotropic hormone refer to the growth hormone produced naturally in animals and extracted from carcasses. Hormone extracted from human cadavers

9945-515: The opposite of the changes that would normally occur over a 10- to 20-year aging period. Despite the fact the authors at no time claimed that GH had reversed the aging process itself, their results were misinterpreted as indicating that GH is an effective anti-aging agent. This has led to organizations such as the controversial American Academy of Anti-Aging Medicine promoting the use of this hormone as an "anti-aging agent". A Stanford University School of Medicine meta-analysis of clinical studies on

10062-433: The optic nerves, or cause deficiency of other pituitary hormones by displacement. Prolonged GH excess thickens the bones of the jaw, fingers and toes, resulting in heaviness of the jaw and increased size of digits, referred to as acromegaly . Accompanying problems can include sweating, pressure on nerves (e.g., carpal tunnel syndrome ), muscle weakness, excess sex hormone-binding globulin (SHBG), insulin resistance or even

10179-415: The patient can produce an immune response against GH. GH may also be a risk factor for Hodgkin's lymphoma . One survey of adults that had been treated with replacement cadaver GH (which has not been used anywhere in the world since 1985) during childhood showed a mildly increased incidence of colon cancer and prostate cancer, but linkage with the GH treatment was not established. The first description of

10296-475: The peptides growth hormone-releasing hormone (GHRH or somatocrinin ) and growth hormone-inhibiting hormone (GHIH or somatostatin ) into the hypophyseal portal venous blood surrounding the pituitary. GH release in the pituitary is primarily determined by the balance of these two peptides, which in turn is affected by many physiological stimulators (e.g., exercise, nutrition, sleep) and inhibitors (e.g., free fatty acids) of GH secretion. Somatotropic cells in

10413-414: The protein from degradation. In most cases, organisms containing recombinant DNA have apparently normal phenotypes . That is, their appearance, behavior and metabolism are usually unchanged, and the only way to demonstrate the presence of recombinant sequences is to examine the DNA itself, typically using a polymerase chain reaction (PCR) test. Significant exceptions exist, and are discussed below. If

10530-401: The protein was obtained by processing large quantities of human blood from multiple donors, which carried a very high risk of transmission of blood borne infectious diseases , for example HIV and hepatitis B. Hepatitis B infection can be successfully controlled through the use of a recombinant subunit hepatitis B vaccine , which contains a form of the hepatitis B virus surface antigen that

10647-427: The rDNA sequences encode a gene that is expressed, then the presence of RNA and/or protein products of the recombinant gene can be detected, typically using RT-PCR or western hybridization methods. Gross phenotypic changes are not the norm, unless the recombinant gene has been chosen and modified so as to generate biological activity in the host organism. Additional phenotypes that are encountered include toxicity to

10764-508: The rate of about 700 μg/day, while healthy adults secrete GH at the rate of about 400 μg/day. Sleep deprivation generally suppresses GH release, particularly after early adulthood. Stimulators of growth hormone (GH) secretion include: Inhibitors of GH secretion include: In addition to control by endogenous and stimulus processes, a number of foreign compounds ( xenobiotics such as drugs and endocrine disruptors ) are known to influence GH secretion and function. Effects of growth hormone on

10881-411: The rearrangement of the clusters. Boyle argued that matter's basic elements consisted of various sorts and sizes of particles, called "corpuscles", which were capable of arranging themselves into groups. In 1789, William Higgins published views on what he called combinations of "ultimate" particles, which foreshadowed the concept of valency bonds . If, for example, according to Higgins, the force between

10998-546: The regularity of repeating unit-cellular-structure that characterizes salts, covalent crystals, and metals. Molecules are generally held together by covalent bonding . Several non-metallic elements exist only as molecules in the environment either in compounds or as homonuclear molecules, not as free atoms: for example, hydrogen. While some people say a metallic crystal can be considered a single giant molecule held together by metallic bonding , others point out that metals behave very differently than molecules. A covalent bond

11115-630: The requirement for intravenous total parenteral nutrition . In 1990, the US Congress passed an omnibus crime bill, the Crime Control Act of 1990 , that amended the Federal Food, Drug, and Cosmetic Act , that classified anabolic steroids as controlled substances and added a new section that stated that a person who "knowingly distributes, or possesses with intent to distribute, human growth hormone for any use in humans other than

11232-544: The rest of the Nutropin line). Recombinant DNA Recombinant DNA ( rDNA ) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning ) that bring together genetic material from multiple sources, creating sequences that would not otherwise be found in the genome . Recombinant DNA is the general name for a piece of DNA that has been created by combining two or more fragments from different sources. Recombinant DNA

11349-518: The restriction of HGH therapy to the treatment of idiopathic short stature. Very limited clinical studies of growth hormone derived from an Old World monkey, the rhesus macaque , were conducted by John C. Beck and colleagues in Montreal, in the late 1950s. The study published in 1957, which was conducted on "a 13-year-old male with well-documented hypopituitarism secondary to a crainiophyaryngioma," found that: "Human and monkey growth hormone resulted in

11466-405: The same atoms in different arrangements are called isomers . Also carbohydrates, for example, have the same ratio (carbon:hydrogen:oxygen= 1:2:1) (and thus the same empirical formula) but different total numbers of atoms in the molecule. The molecular formula reflects the exact number of atoms that compose the molecule and so characterizes different molecules. However different isomers can have

11583-404: The same atomic composition while being different molecules. The empirical formula is often the same as the molecular formula but not always. For example, the molecule acetylene has molecular formula C 2 H 2 , but the simplest integer ratio of elements is CH. The molecular mass can be calculated from the chemical formula and is expressed in conventional atomic mass units equal to 1/12 of

11700-405: The same length and strength, which yields a molecular structure as shown below: The science of molecules is called molecular chemistry or molecular physics , depending on whether the focus is on chemistry or physics. Molecular chemistry deals with the laws governing the interaction between molecules that results in the formation and breakage of chemical bonds, while molecular physics deals with

11817-572: The same time different biochemical activities. Molecular spectroscopy deals with the response ( spectrum ) of molecules interacting with probing signals of known energy (or frequency , according to the Planck relation ). Molecules have quantized energy levels that can be analyzed by detecting the molecule's energy exchange through absorbance or emission . Spectroscopy does not generally refer to diffraction studies where particles such as neutrons , electrons, or high energy X-rays interact with

11934-517: The smallest particles of pure chemical substances that still retain their composition and chemical properties. This definition often breaks down since many substances in ordinary experience, such as rocks , salts , and metals , are composed of large crystalline networks of chemically bonded atoms or ions , but are not made of discrete molecules. The modern concept of molecules can be traced back towards pre-scientific and Greek philosophers such as Leucippus and Democritus who argued that all

12051-537: The subject published in early 2007 showed that the application of GH on healthy elderly patients increased muscle by about 2 kg and decreased body fat by the same amount. However, these were the only positive effects from taking GH. No other critical factors were affected, such as bone density, cholesterol levels, lipid measurements, maximal oxygen consumption, or any other factor that would indicate increased fitness. Researchers also did not discover any gain in muscle strength, which led them to believe that GH merely let

12168-628: The third and fourth NREM sleep stages. Surges of secretion during the day occur at 3- to 5-hour intervals. The plasma concentration of GH during these peaks may range from 5 to even 45 ng/mL. Between the peaks, basal GH levels are low, usually less than 5 ng/mL for most of the day and night. Additional analysis of the pulsatile profile of GH described in all cases less than 1 ng/ml for basal levels while maximum peaks were situated around 10-20 ng/mL. A number of factors are known to affect GH secretion, such as age, sex, diet, exercise, stress, and other hormones. Young adolescents secrete GH at

12285-421: The three widely used methods for diagnosing HIV infection has been developed using recombinant DNA. The antibody test ( ELISA or western blot ) uses a recombinant HIV protein to test for the presence of antibodies that the body has produced in response to an HIV infection. The DNA test looks for the presence of HIV genetic material using reverse transcription polymerase chain reaction (RT-PCR). Development of

12402-430: The tissues of the body can generally be described as anabolic (building up). Like most other peptide hormones, GH acts by interacting with a specific receptor on the surface of cells. Increased height during childhood is the most widely known effect of GH. Height appears to be stimulated by at least two mechanisms: In addition to increasing height in children and adolescents, growth hormone has many other effects on

12519-543: The treatment of a disease or other recognized medical condition, where such use has been authorized by the Secretary of Health and Human Services" has committed a felony . The Drug Enforcement Administration of the US Department of Justice considers off-label prescribing of HGH to be illegal, and to be a key path for illicit distribution of HGH. This section has also been interpreted by some doctors, most notably

12636-668: The ultimate particle of oxygen and the ultimate particle of nitrogen were 6, then the strength of the force would be divided accordingly, and similarly for the other combinations of ultimate particles. Amedeo Avogadro created the word "molecule". His 1811 paper "Essay on Determining the Relative Masses of the Elementary Molecules of Bodies", he essentially states, i.e. according to Partington 's A Short History of Chemistry , that: The smallest particles of gases are not necessarily simple atoms, but are made up of

12753-409: The universe is composed of atoms and voids . Circa 450 BC Empedocles imagined fundamental elements ( fire ( [REDACTED] ), earth ( [REDACTED] ), air ( [REDACTED] ), and water ( [REDACTED] )) and "forces" of attraction and repulsion allowing the elements to interact. A fifth element, the incorruptible quintessence aether , was considered to be the fundamental building block of

12870-523: The use of DNA technology are found in essentially every pharmacy, physician or veterinarian office, medical testing laboratory, and biological research laboratory. In addition, organisms that have been manipulated using recombinant DNA technology, as well as products derived from those organisms, have found their way into many farms, supermarkets , home medicine cabinets , and even pet shops, such as those that sell GloFish and other genetically modified animals . The most common application of recombinant DNA

12987-420: The use of GH and will issue sanctions against athletes who are caught using it. However, because GH is a potent endogenous protein, it is very difficult to detect GH doping. In the United States, GH is legally available only by prescription from a medical doctor. To capitalize on the idea that GH might be useful to combat aging, companies selling dietary supplements have websites selling products linked to GH in

13104-475: The use of GH as a doping agent was Dan Duchaine's "Underground Steroid handbook" which emerged from California in 1982; it is not known where and when GH was first used this way. Athletes in many sports have used human growth hormone in order to attempt to enhance their athletic performance. Some recent studies have not been able to support claims that human growth hormone can improve the athletic performance of professional male athletes. Many athletic societies ban

13221-434: The use of these transgenic crops have not been fully resolved. The idea of recombinant DNA was first proposed by Peter Lobban, a graduate student of Prof. Dale Kaiser in the Biochemistry Department at Stanford University Medical School. The first publications describing the successful production and intracellular replication of recombinant DNA appeared in 1972 and 1973, from Stanford and UCSF . In 1980 Paul Berg ,

13338-432: The vaporization/sublimation of such materials does produce separate molecules where electrons are still transferred fully enough for the bonds to be considered ionic rather than covalent. Most molecules are far too small to be seen with the naked eye, although molecules of many polymers can reach macroscopic sizes, including biopolymers such as DNA . Molecules commonly used as building blocks for organic synthesis have

13455-536: The world's population. Golden rice is not currently in use, pending the resolution of regulatory and intellectual property issues. Commercial varieties of important agricultural crops (including soy, maize/corn, sorghum, canola, alfalfa and cotton) have been developed that incorporate a recombinant gene that results in resistance to the herbicide glyphosate (trade name Roundup ), and simplifies weed control by glyphosate application. These crops are in common commercial use in several countries. Bacillus thuringiensis

13572-466: Was learning the Dalton hook-and-eye bonding method , which was the mainstream description of bonds between atoms at the time. Pauling, however, was not satisfied with this method and looked to the newly emerging field of quantum physics for a new method. In 1926, French physicist Jean Perrin received the Nobel Prize in physics for proving, conclusively, the existence of molecules. He did this by calculating

13689-497: Was widely observed until the US National Institutes of Health developed and issued formal guidelines for rDNA work. Today, recombinant DNA molecules and recombinant proteins are usually not regarded as dangerous. However, concerns remain about some organisms that express recombinant DNA, particularly when they leave the laboratory and are introduced into the environment or food chain. These concerns are discussed in

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