Tuesday, March 17, 2020

buy custom Understanding Gene Therapy essay

buy custom Understanding Gene Therapy essay Introduction Genes are the basic physical and functional units that enhance heredity. They are capable of encoding instructions that guide processing of proteins by the body (Yashon Cummings, 2012). The processed proteins facilitate most of the life functions and form a better percentage of the cellular structures. When genes are altered, the encoded proteins are rendered ineffective and unable to function normally. This is what causes genetic disorder in a person. According to studies that have been conducted, almost everybody unconsciously carries some defective genes (Giacca, 2010). Lately, there has been increasing attention to the treatment of genetic metabolic diseases. These are diseases that develop as a result of defective genes that cause enzymes to be either absent or generally ineffective and inefficient. Enzymes function in the human body to catalyze metabolic reactions (Giacca, 2010). When these enzymes are ineffective, metabolic processes are slowed down or just fail to take place . This paper seeks to discuss gene therapy, illustrate examples of this treatment approach, discuss the risks and complications, associated with it, and outline some of the ethical principles that guide gene therapy as a method of treatment of genetic disorders. Definition and Understanding of Gene Therapy Gene therapy has been developed to help treat the genetic disorders that result from dysfunctional enzymes. Gene therapy is, thus, a treatment approach that involves replacement of faulty or absent genes with working ones so that the body is able to effectively process and produce correct enzymes or proteins and consequently be able to deal with the root cause of a genetic disease (Kelly, 2007). It is a process that involves introduction of normal and functional genes into the cells of a person, which carry the defective genes so as to enhance reconstitution of the missing protein product. It is a medical treatment process that helps in the correction of a deficient phenotype so that the normal amount of gene products is synthesized by the body. The first gene therapy trial was performed by French Anderson and R. Michael Blaese on a four year old girl in 1990 (Kelly, 2007). In order to perform gene therapy, somatic cells are modified by transferring desired gene sequences into the ge nome. However, for this to succeed, somatic cells are required to ensure that the genes that are inserted to correct the disorder are not carried down to the following generations. Examples of Gene Therapy Gene therapy has been applied widely in the treatment of genetic disorders. This is because almost all cells in the human body contain genes. This makes genetic therapy feasible in virtually all cells of the human body. Gene therapy has been performed in the cells of the body and the ovum or sperm cells. There are, thus, two broad examples of gene therapy; the somatic cell gene therapy and the germ line cell therapy. Somatic Cell Gene Therapy Somatic cell gene therapy entails introduction of genes into body cells or tissues in order to treat a disease in an individual that has been medically diagnosed to have genetic associations or origin (Wintrobe Greer, 2009). This enhances expression of an exogenous functional gene into another persons somatic cells. This genetic therapeutic approach is considered to be non-reproductive since somatic cells, where it is involved are not reproductive cells. There is consensus that this gene cell therapy is safer than other approaches because it only has influence on the targeted cells in the patient. The introduced cells are not, therefore, passed down to the future generations. The effects of a somatic cell gene therapy end with the individual who is treated. This implies that the genetic disorders that are treated through the application of somatic cell gene therapy do not have a bearing on the children of the patient. Somatic cell gene therapy is used to correct errors, relating to metabolism. For example, phenilketonuria has been treated through somatic cell gene therapy. This disorder results from the bodys inability to metabolize phenylalanine. The therapy facilitates elimination of the amino acid. Although this therapy is applicable, it does not address all inborn errors, related to metabolism (Kelly, 2007). In the case of a disorder resulting from abnormal alleles for an essential enzyme that leads to deficient metabolic functions, somatic cell gene therapy has been successfully applied as a treatment strategy. In this treatment practice, a copy of gene, capable of expressing the essential enzyme and enhancing the required metabolic function, is introduced. The cloning genes that are involved in the genetic metabolic dysfunction/disorder are identified. The normal genes are, then, introduced into the prover cell within the body, especially in the area, where metabolism is required, while cont rolling the expression of the gene within the limits of the therapeutic and safe levels (Brown, 2010). There are two sub-examples of the somatic cell gene therapy; the ex vio and the in vivo. The in vivo method involves changing of the cells within the body of the patient. The genes are transferred to cells within the body of the patient. This transfer of desired genes inside the patients body led to the derived name of this method. The ex vivo somatic cell gene therapy involves exterior-focused therapeutic approach (Benigni Remuzzi, 2008). The cells of the body are modified outside the body before they are transferred back into the body again. In some therapeutic trials, the cells from the patients own blood or even the bone marrow are removed, grown in the laboratory for some time before they are transplanted back. During this process, the cells are exposed to the virus that carries the targeted gene. The entry of the virus into the cells enhances insertion of the target gene into the DNA of the cell. The cells are, then, given time to grow in the laboratory before they are again t ransferred into the body of the patient through venal injection (Kelly, 2007). This example of somatic cell gene therapy is referred to as ex vivo because the cells are treated outside the body. Germ line Gene Therapy Germ line gene therapy is a treatment approach that involves delivery of gene to sperm or egg or directly into the cells that are responsible for their production. This example of gene therapy might help in preventing defective genes from being transferred to the subsequent generations. The act of modifying genes at the initial stages of embryonic development is also preferred since it serves as a way of correcting defective genes both in the germ line and within the cells of the body (Wintrobe Greer, 2009). In cases when the germ line gene therapy is carried out in the early embryologic stages like during pre-implantation diagnosis and in the vitro fertilization, genetic transfer could be affected in every cell within the developing embryo. However, there are reservations with the germ line gene therapy. This is because of its risks, especially with the possibility of a permanent therapeutic effect that may affect the following generations through genetic inheritance. Risks, associated with Gene Therapy The risks, associated with gene therapy, are various. These risks relate to the way, in which the genes are delivered. The normal genes that replace defective ones, in a gene therapy process, are usually delivered through carriers, which are normally vectors. Most of these vectors are viruses, which researchers use due to their unique ability to carry genetic material into the cells of a gene (Hutter, 2010). This poses a great potential for risks. To begin with, since gene therapy involves introduction of new foreign cell into the system, the body is bound to react through its immune system. The virus that is introduced into the body through gene therapy may cause the immune system to react and attack the new cell in the same way it reacts to other pathogenic and disease-causing organisms or cells. Such immune responses may not only cause complications in the bodys immunity but also lead to other medical and health complications such as inflammation, toxicity and organ failure in som e extreme instances. Gene therapy can also lead to viral spread. The process involves use of viruses to transfer the desired gene into the body. Hutter (2010) cited that since viruses have the capability of affecting more than one type of body cells, there is a possibility that viral vectors that are used in genetic transfer may end up infecting cells other than the targeted cells. All the cells that contain mutated or missing genes may, thus, be affected. This can be a very unfortunate occurrence since even the healthy cells may end up being affected by the vector-carrying virus. Thus, gene therapy may lead to viral spread, which, in turn, might cause other health complications and spread diseases or illnesses including cancer (Hutter, 2010). Perhaps, one of the greatest risks, associated with gene therapy, is the possibility of the virus to reverse to its original form. Viruses are used to transfer the required genes into the body cells to replace the defective ones that are causing enzyme and other somatic dysfunctions. However, the viruses that are used as vectors or carriers of the desired gene may recover their initial viral and infection ability and cause diseases, once they are introduced into the body through gene therapy (Abraham, 2008). This possibility is quite unfortunate given that gene therapy in itself is originally meant to be a treatment method, which should not lead to the spread of other diseases in the process of treating another disease. The risks of gene therapy have been registered, especially with regard to the ability of the virus to spread and induce tumor formation within the genome (Kelly, 2007). Scientists and researchers have registered their reservations and concerns that if the new genes get inserted or introduced in the wrong spot within the genome, there are chances that the insertion may cause tumor formation (Kelly, 2007). This has been observed by geneticists and scientists in some of the laboratory clinical trials. Besides, the new DNA that is introduced into the body during treatment through gene therapy may end up affecting the reproductive cells of the patient, especially where germ line gene therapy is involved. This may cause changes in the genetic composition and affect the children that are born after one is treated through gene therapy. Complications with Gene Therapy Although trials of gene therapy have significantly been successful, there are a few reservations that have been reported. The few complications that scientific and genetic researchers have realized with gene therapy relate to the medical and health issues that gene therapy as a treatment procedure might cause in a patient. For example, gene therapy has been associated with T-cell leukemia (Abraham, 2008). When the retroviral vector was inserted inappropriately near the proto-oncogene LMO2, the result was a proliferation of uncontrolled mature T cells, which causes T-cell leukemia in a patient. This complication is caused by the lack of both the B and T cells (Gibbs, 1996). Such a complication that result from gene therapy may expose a patient to further medical complications, including the use of bone marrow transplant that is retrieved from a histocompatible sibling of the patient. Unfortunately, this is often not easy to secure or procure. Thus, gene therapy may lead to other compl ications, some of which are very severe and can even be fatal. Gene therapy may lead to interruption of important genetic sequence and harm the cell instead of resolving the genetic and cellular defects that the treatment targets. This is because the retroviruses that penetrate the immune defenses into the target cells often affect the cells in an unpredictable manner. Abraham (2008) cited that the retroviruses may even insert the therapeutic gene at unpredictable position within the cells DNA. This is what might lead to interruption of very important genetic sequences that might have been going on within the cells DNA. Even in the cases, where gene therapy succeeds, the new genes always end up in the dormant parts of the cells DNA (Brown, 2010). In the dormant stretches, the new genes often do not get switched on as frequent enough to be able to make the much required genetic difference in the patient who is undergoing treatment (Gibbs, 1996). Ethical Concerns, surrounding Gene Therapy Gene therapy is a medical treatment involving alteration of the bodys set of basic genetic messages. Since it touches on the very processes that guide life and its characteristics, this treatment approach has raised and continues to raise various ethical issues. One of the ethical concerns that gene therapy is raising is its fairness in terms of the use of the genetic information that is disclosed during the diagnosis and treatment procedures. There are concerns, relating to the use of the genetic information (Cummings, 2009). For example, many people are in a dilemma with regard to the person who should be entitled to the access to the personal genetic information of the patient and how such information will be used. There are concerns about the privacy and confidentiality of the genetic information that is retrieved in the course of gene therapy. Since it is private and personal information, pressure is piling on the need to keep genetic information very private and confidential un der all circumstances. Genetic therapy is often associated with stigmatization. The psychological impact that is created by a persons genetic difference should, thus, be well taken care of before gene therapy is approved. For example, there are concerns about the perceptions of the society towards an individual who undergoes gene therapy. The members of the minority communities are particularly vulnerable to social stigma, associated with gene therapy. Besides, being a complex procedure that has great potentials for risks and complications, there is need to seek adequate informed consent from the patient and the family members before gene therapy is carried out on a patient. This is because gene therapy has very close link and relationship to the reproductive aspects of an individual (Cummings, 2009). The healthcare personnel, thus, need to carefully counsel the patient and the family members about the risks, the limitations and the implications of gene therapy. This ethical aspect is very essential given the clinical issues, uncertainties, complications and risks that are associated with gene therapy. Conclusion Gene therapy is increasingly becoming acceptable and a popular method for treatment of genetic disorders and gene-related diseases and illnesses. Although germ line gene therapy exists, it is still outlawed in most states like the entire European Union because of its implications. Somatic cell gene therapy is, however, acceptably practiced as a treatment method. However, the complications and risks that are associated with gene therapy still limit its use considerably. Thus, there is a need for scientists to evaluate further the safe, effective and efficient ways of using gene therapy as a treatment procedure for genetic disorders giving careful attention to the ethical concerns that this procedure raises. Buy custom Understanding Gene Therapy essay

Sunday, March 1, 2020

USS Pennsylvania (BB-38) in World War II

USS Pennsylvania (BB-38) in World War II Commissioned in 1916, USS Pennsylvania (BB-38) proved to be a workhorse for the US Navys surface fleet for over thirty years.   Taking part in World War I (1917-1918), the battleship later survived the Japanese attack on Pearl Harbor and saw extensive service across the Pacific during World War II (1941-1945).   With the end of the war, Pennsylvania provided a final service as a target ship during the 1946 Operation Crossroads atomic testing. A New Design Approach After designing and constructing five classes of dreadnought battleships, the US Navy concluded that future ships should make use of a set of standardized tactical and operational traits. This would allow these vessels to operate together in combat and would simplify logistics. Designated the Standard-type, the next five classes were propelled by  oil-fired boilers rather than coal, saw the removal of amidships turrets, and utilized an â€Å"all or nothing† armor scheme.   Among these alterations, the transition to oil was made with the goal of increasing the vessel’s range as the US Navy believed this would be critical in any future naval war with Japan. The new all or nothing armor arrangement called for critical areas of the vessel, such as magazines and engineering, to be heavily armored while less important spaces were left unprotected. Also, Standard-type battleships were to be capable of a  minimum top speed of 21 knots and have a tactical turn radius of 700 yards.   Construction Incorporating these design characteristics, USS Pennsylvania (BB-28) was laid down at the Newport News Shipbuilding and Drydock Company on October 27, 1913. The lead ship of its class, its design came about following the US Navys General Board ordering a new class of battleships in 1913 which mounted twelve 14 guns, twenty-two 5 guns, and an armor scheme similar to the earlier Nevada-class. The Pennsylvania-class main guns were to be mounted in four triple turrets while propulsion was to be provided by steam driven geared turbines turning four propellers. Increasingly concerned about improvements in torpedo technology, the US Navy directed that the new ships utilize a four layer system of armor. This employed multiple layers of thin plate, separated by air or oil, outboard of the main armor belt. The goal of this system was to dissipate the explosive force of a torpedo before it reached the ships primary armor. World War I Launched on March 16, 1915 with Miss Elizabeth Kolb as its sponsor, Pennsylvania was commissioned the follow year on June 16. Joining the US Atlantic Fleet, with Captain Henry B. Wilson in command, the new battleship became the commands flagship that October when Admiral Henry T. Mayo transferred his flag on board. Operating off the East Coast and in the Caribbean for the remainder of the year, Pennsylvania returned to Yorktown, VA in April 1917 just as the United States entered World War I. As the US Navy began deploying forces to Britain, Pennsylvania remained in American waters as it used fuel oil rather than coal like many of the Royal Navys vessels. Since tankers could not be spared to transport fuel abroad, Pennsylvania and the US Navys other oil-fired battleships conducted operations off the East Coast for the duration of the conflict. In December 1918, with the war ended, Pennsylvania escorted President Woodrow Wilson, aboard SS George Washington, to France for the Paris Peace Conference. USS Pennsylvania (BB-38) Overview Nation: United StatesType: BattleshipShipyard: Newport News Shipbuilding Drydock CompanyLaid Down: October 27, 1913Launched: March 16, 1915Commissioned: June 12, 1916Fate: Scuttled February 10, 1948 Specifications (1941) Displacement: 31,400 tonsLength: 608 ft.Beam: 97.1 ft.Draft: 28.9 ft.Propulsion: 4 propellers driven by 1 Ãâ€" Bureau Express and 5 Ãâ€" White-Forster boilersSpeed: 21 knotsRange: 10,688 miles at 15 knotsComplement: 1,358 men Armament Guns 12 Ãâ€" 14 in. (360 mm)/45 cal guns (4 triple turrets)14 Ãâ€" 5 in./51 cal. guns12 Ãâ€" 5 in./25 cal. anti-aircraft guns Aircraft 2 x aircraft Interwar Years The remaining flagship of the US Atlantic Fleet, Pennsylvania operating in home waters in early 1919 and that July met the returning George Washington and escorted it into New York. The next two years saw the battleship conduct routine peacetime training until receiving orders to join the US Pacific Fleet in August 1922. For the next seven years, Pennsylvania operated on the West Coast and participated in training around Hawaii and the Panama Canal. The routine of this period was punctuated in 1925 when the battleship conducted a goodwill tour to New Zealand and Australia. In early 1929, after training exercises off Panama and Cuba, Pennsylvania sailed north and entered the Philadelphia Navy Yard for an extensive modernization program. Remaining at Philadelphia for almost two years, the ships secondary armament was modified and its cage masts replaced by new tripod masts. After conducting refresher training off Cuba in May 1931, ​Pennsylvania returned to the Pacific Fleet. In the Pacific For the next decade, Pennsylvania remained a stalwart of the Pacific Fleet and took part in annual exercises and routine training. Overhauled at Puget Sound Naval Shipyard in late 1940, it sailed for Pearl Harbor on January 7, 1941. Later that year, Pennsylvania was one of fourteen ships to receive the new CXAM-1 radar system. In the fall of 1941, the battleship was dry docked at Pearl Harbor. Though scheduled to leave on December 6, Pennsylvanias departure was delayed. As a result, the battleship remained in dry dock when the Japanese attacked the next day. One of the first ships to respond with anti-aircraft fire, Pennsylvania took minor damage during the attack despite repeated Japanese attempts to destroy the dry docks caisson. Positioned forward of the battleship in the drydock, the destroyers USS Cassin and USS Downes were both severely damaged. World War II Begins In the wake of the attack, Pennsylvania departed Pearl Harbor on December 20 and sailed for San Francisco. Arriving, it underwent repairs before joining a squadron led by Vice Admiral William S. Pye which operated off the West Coast to prevent a Japanese strike. Following the victories at Coral Sea and Midway, this force was disbanded and Pennsylvania briefly returned to Hawaiian waters. In October, with the situation in the Pacific stabilized, the battleship received orders to sail for Mare Island Naval Shipyard and a major overhaul. While at Mare Island, Pennsylvanias tripod masts were removed and its anti-aircraft armament enhanced with the installation of ten Bofors 40 mm quad mounts and fifty-one Oerlikon 20 mm single mounts. In addition, the existing 5 guns were replaced with new rapid fire 5 guns in eight twin mounts. Work on Pennsylvania was completed in February 1943 and following refresher training, the ship departed for service in the Aleutian Campaign in late April. In the Aleutians Reaching Cold Bay, AK on April 30, Pennsylvania joined Allied forces for the liberation of Attu. Bombarding enemy shore positions on May 11-12, the battleship supported Allied forces as they went ashore. Later on May 12, Pennsylvania evaded a torpedo attack and its escorting destroyers succeeded in sinking the perpetrator, the submarine I-31, the next day. Aiding in operations around the island for the remainder of the month, Pennsylvania then retired to Adak. Sailing in August, the battleship served as Rear Admiral Francis Rockwells flagship during the campaign against Kiska. With the successful re-capture of the island, the battleship became flagship of Rear Admiral Richmond K. Turner, Commander Fifth Amphibious Force, that fall. Sailing in November, Turner re-captured Makin Atoll later that month. Island Hopping On January 31, 1944, Pennsylvania took part in the bombardment prior to the invasion of Kwajalein. Remaining on station, the battleship continued to provide fire support once the landings began the next day. In February, Pennsylvania fulfilled a similar role during the invasion of Eniwetok. After conducting training exercises and a voyage to Australia, the battleship joined Allied forces for the Marianas Campaign in June. On June 14, Pennsylvanias guns pounded enemy positions on Saipan in preparation for landings the next day. Remaining in the area, the vessel struck targets on Tinian and Guam as well as provided direct fire support to troops ashore on Saipan. The following month, Pennsylvania aided in the liberation of Guam. With the end of operations in the Marianas, it joined the Palau Bombardment and Fire Support Group for the invasion of Peleliu in September. Remaining off the beach, Pennsylvanias main battery pummeled Japanese positions and greatly aided Allied forces ashore. Surigao Strait Following repairs in the Admiralty Islands in early October, Pennsylvania sailed as part of Rear Admiral Jesse B. Oldendorfs Bombardment and Fire Support Group which in turn was part of Vice Admiral Thomas C. Kinkaids Central Philippine Attack Force. Moving against Leyte, Pennsylvania reached its fire support station on October 18 and began covering General Douglas MacArthurs troops as they went ashore two days later. With the Battle of Leyte Gulf underway, Oldendorfs battleships moved south on October 24 and blocked the mouth of the Surigao Strait. Attacked by Japanese forces that night, his vessels sank the battleships Yamashiro and Fuso. In the course of the fighting, Pennsylvanias guns remained quiet as its older fire control radar could not distinguish the enemy vessels in the confined waters of the strait. Retiring to the Admiralty Islands in November, Pennsylvania returned to action in January 1945 as part of Oldendorfs Lingayen Bombardment and Fire Support Group. Philippines Driving off air attacks on January 4-5, 1945, Oldendorfs ships began striking targets around the mouth of Lingayen Gulf, Luzon the next day. Entering the gulf on the afternoon of January 6, Pennsylvania commenced reducing Japanese defenses in the area. As in the past, it continued to offer direct fire support once Allied troops began landing on January 9. Commencing a patrol of the South China Sea a day later, Pennsylvania returned after a week and remained in the gulf until February. Withdrawn on February 22, it steamed for San Francisco and an overhaul. While at the Hunters Point Shipyard, Pennsylvanias main guns received new barrels, the anti-aircraft defenses were enhanced, and new fire control radar was installed. Departing on July 12, the ship sailed for newly captured Okinawa with stops at Pearl Harbor and to bombard Wake Island. Okinawa Reaching Okinawa in early August, Pennsylvania anchored in Buckner Bay near USS Tennessee (BB-43). On August 12, a Japanese torpedo plane penetrated the Allied defenses and stuck the battleship in the stern. The torpedo strike opened a thirty-foot hole in Pennsylvania and badly damaged its propellers. Towed to Guam, the battleship was dry docked and received temporary repairs. Leaving in October, it transited the Pacific en route to Puget Sound. While at sea, the Number 3 propeller shaft broke necessitating divers to cut it and the propeller away. As a result, Pennsylvania limped into Puget Sound on October 24 with only one operable propeller. Final Days As World War II had ended, the US Navy did not intend to retain Pennsylvania. As a result, the battleship received only those repairs necessary for transit to the Marshall Islands. Taken to Bikini Atoll, the battleship was used as a target vessel during the Operation Crossroads atomic tests in July 1946. Surviving both blasts, Pennsylvania was towed to Kwajalein Lagoon where it was decommissioned on August 29. The ship remained in the lagoon until early 1948 where it was used for structural and radiological studies. On February 10, 1948, Pennsylvania taken from the lagoon and sunk at sea.