Human genetic engineering
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It holds the promise of curing genetic diseases like cystic fibrosis. Gene therapy has been successfully used to treat multiple diseases, including X-linked SCID, chronic lymphocytic leukemia (CLL), and Parkinson's disease. In 2012, Glybera became the first gene therapy treatment to be approved for clinical use in either Europe or the United States after its endorsement by the European Commission.
It is speculated that genetic engineering could be used to change physical appearance, metabolism, and even improve physical capabilities and mental faculties like memory and intelligence, although for now these uses are limited to science fiction.
Gene therapy trials on humans began in 2004 on patients with severe combined immunodeficiency (SCID). In 2000, the first gene therapy "success" resulted in SCID patients with a functional immune system. These trials were stopped when it was discovered that two of ten patients in one trial had developed leukemia resulting from the insertion of the gene-carrying retrovirus near an oncogene. In 2007, four of the ten patients had developed leukemia. Work is now focusing on correcting the gene without triggering an oncogene. Since 1999, gene therapy has restored the immune systems of at least 17 children with two forms (ADA-SCID and X-SCID) of the disorder.
Human genetic engineering is already being used on a small scale to allow infertile women with genetic defects in their mitochondria to have children. The technique, known as ooplasmic transfer, is used to inject the mitochondria from the donor's egg cell into the egg of the infertile woman. In vitro fertilization is performed on the egg.  Healthy human eggs from a second mother are used. The first mother thus contributes the 23 chromosomes of the nuclear genome, which contain the majority of the child's genetic information, while the second mother contributes the mitochondrial genome, which contains 37 genes. The child produced this way has genetic information from two mothers and one father. The changes made are germline changes and will likely be passed down from generation to generation, and, thus, are a permanent change to the human genome.
Other forms of human genetic engineering are still theoretical. Recombinant DNA research is usually performed to study gene expression and various human diseases. This includes the creation of transgenic animals, such as mice.
Genetic engineering can be broken down into two applications, somatic and germline. Both processes involve changing the genes in a cell through the use of a vector carrying the gene of interest. The new gene may be integrated into the cell’s genetic material through recombination, or may remain separate from the genome, such as in the form of a plasmid. If integrated into the genome, it may recombine at a random location or at a specific location (site-specific recombination) depending on the technology used.
Somatic cell therapy
As the name suggests, somatic cell therapy alters the genome of somatic cells. This process targets specific organs and tissues in a person. The aim of this technique is to correct a mutation or provide a new function in human cells. If successful, somatic cell therapy has the potential to treat genetic disorders with few therapeutic options. This process does not affect the genetics of gametic cells within the same body. Any genetic modifications are restricted to a patient individually and cannot be passed on to their offspring.
Several somatic cell gene transfer experiments are currently in clinical trials with varied success. Over 600 clinical trials utilizing somatic cell therapy are underway in the United States. Most of these trials focus on treating severe genetic disorders, including immunodeficiencies, haemophilia, thalassaemia, and cystic fibrosis. These disorders are good candidates for somatic cell therapy because they are caused by single gene defects. While somatic cell therapy is promising for treatment, a complete correction of a genetic disorder or the replacement of multiple genes in somatic cells is not yet possible. Only a few of the many clinical tries are in the advanced stages.
Germline cell therapy
Germline cell therapy alters the genome of germinal cells. Specifically, it targets eggs, sperm, and very early embryos. Genetic changes made to germline cells affect every cell in the resulting individual’s body and can also be passed on to their offspring. The practice of germline cell therapy is currently banned in several countries, but has not been banned in the US.
Theoretically, germline cell therapy could treat or cure individuals who are predisposed to certain genetic disorders before birth. This process has not been attempted on humans, but has been applied to some plants and various animal species.. Several problems have arisen with this method, including only partial or multiple insertions of the desired gene, inaccurate placing of the desired gene in to the genome, and interference with other critical genes in the genome. While most defects are detectable in embryos, it is likely that some would be overlooked. Animal studies have shown that gene transformations involving the early embryo can be more effective than somatic cell transformations. However, attempts of germline cell transfer on human embryos will not be attempted unless the inefficient transformation that occurs during germline cell therapy is overcome.
|This section is outdated. (July 2013)|
|SCID-X1||MMLV vector||completed, ongoing|
|Leukemia||HIV vector||"Wild success" (on a small population)|
Policies on genetic modification tend to fall in the realm of general guidelines about human-involved biomedical research. Universal restrictions and documents have been made by international organizations to set a general standard on the issue of involving humans directly in research.
One key regulation comes from the Declaration of Helsinki (Ethical Principles for Medical Research Involving Human Subjects), last amended by at the World Medical Association’s General Assembly in 2008. This document focuses on the principles physicians and researchers must consider when involving humans as the research subject. Additionally, the Statement on Gene Therapy Research initiated by the Human Genome Organization in 2001 also provides a legal baseline for all countries. HUGO’s document reiterates the organization’s common principles researchers must follow when conducting human genetic research including the recognition of human freedom and adherence to human rights, and the statement also declares recommendations for somatic gene therapy including a call for researchers and governments to attend to public concerns about the pros, cons and ethical concerns about the research.
No federal legislation specifically lays out protocol and restrictions about either germline or somatic human genetic engineering. Instead, this subject is governed by overlapping regulations from local and federal agencies. Included agencies, from the Department of Health and Human Services, are the Food and Drug Administration and the Recombinant DNA Advisory Committee of the National Institutes of Health. Additionally, researchers who wish to receive federal funds when conducting research about an investigational new drug application, which is commonly the case for somatic human genetic engineering, are required to obey international and federal guidelines dealing with the protection of human test subjects.
The National Institutes of Health (NIH) mainly serves as the gene therapy regulator for federally funded research institutions and projects. Privately funded human genetic research can only be recommended to voluntarily follow their regulations. NIH provides funding for lab research that develops or enhances devices utilized in human genetic engineering and to evaluate the ethics and quality of science present in current research labs. The NIH maintains a mandatory registry of human genetic engineering research protocols from all federally funded projects. An advisory committee to the NIH published a set of guidelines on the manipulation of genes. The document for the NIH guidelines discusses safety considerations for the lab as well as for any human patient test subject. A wide range of various experimental types which involve any type of gene transfer or alteration are discussed. Several sections specifically pertain to human genetic engineering including Section III-C-1. This section states the review process researches must undergo and the aspects that are considered when attempting to be approved to begin clinical research involving human genetic transfer into a patient. This document is an important tool required for scientists to follow in order to further scientific progress in the field of somatic cell therapy.
The United States Food and Drug Administration (FDA) regulates the quality and safety of gene therapy products and supervises how these products are implicated clinically. Therapeutic alteration of the human genome falls under the same regulatory requirements as any other medical treatment. Research involving human subjects, such as clinical trials, must be reviewed and approved by the FDA and an Institutional Review Board.
The potential for new technologies and genetic modifications brings along many ethical and moral concerns. Some of these concerns include the belief that every fetus has an inherent right to remain genetically unmodified, the belief that parents hold the rights to modify their unborn offspring, and the belief that every child has the right to be born free from preventable diseases.
The science of genomics is able to identify which genes cause specific diseases. Through genetic testing, it has become much easier to make a diagnosis for many genetic conditions. This testing supplies the ability to test pre-symptomatic individuals, at-risk individuals, and carriers to determine whether they will develop a specific condition. It is particularly useful to people who intend to have children, and want to ensure they will not pass their genetic condition to their offspring. Current advances include preimplantation genetic diagnosis, which allows for embryos to be created in vitro, and only those embryos that are not affected by a specific genetic disorder will be implanted in the woman’s uterus.
Another beneficial aspect of genetic engineering is the potential to cure numerous genetic diseases. The majority of genetic disorders are cause by single point mutations in the DNA. By somatic cell therapy, these diseases can be easily cured. Additionally, the implementation of germline cell therapy can not only cure many other genetic diseases, but can also prevent the passing of the disease to the next generation.
Genetic engineering also allows the potential for human enhancements. Humans value intelligence, beauty, strength, endurance, and certain personality characteristics and behavioral tendencies. If these traits were found to be due to a genetic component, humans could be improved to obtain those traits. Many people try to improve themselves already through diet, exercise, education, cosmetics, and plastic surgery. Humans try to do these things for themselves and parents try to provide these things for their children. Exercising to improve strength, dexterity, and fitness is a worthwhile goal. Pursuing education to increase mental capabilities is considered a praiseworthy act. Accomplishing these goals through genetics could be more efficient and completely worthwhile.
Other arguments made to support HGE include the optimism to control the human genome to address societal issues and expand our knowledge of humans as a species. This view sees the prevention of genetic diseases as a duty to human kind in preventing harm to future generations.
So far the public view of gene therapy is unknown as a general consensus on the matter has not been achieved. The feeling of approval or disapproval among the public shifts from country to country mostly stemming from the depth of education given to the public on the issue. In general most of the fears or disapproval towards human genetic engineering consists of cost effectiveness of the procedures or perceptions of what might happen in the future.
Human genetic engineering promotes a more desired genotype chosen and shaped by the consumer based off personal preference. If human genetic engineering becomes more prevalent among society people will want to give their offspring the best advantages in life which could come in the form of athletics or intelligence. This will lead to a more similar genetic gene pool among the human race as similar traits will be selected for. This lack of genetic variance among humans poses a threat to the resilience of the species if a new illness were to surface. The cost of genetic engineering through IVF can reach from $5,000 to $25,000 and usually multiple attempts are required before successful implantation occurs. The issue that arises from this is that genetic engineering will only be available for those that can afford it. Since the cost for IVF is so high only those of the upper class will be able to afford it while those in the lower class will not have this procedure available. This separation of classes will only broaden with the limited availability of human genetic engineering. Although deaths due to complications of human genetic engineering are rare, there is still a concern about the health risks a person takes upon undergoing this procedure. Health risks not only arise from the genetic engineering procedures themselves, such as IVF, but also from simply the altering of the genes. Determining which genes code for specific phenotypes and how to alter them in order to get the desired phenotype is a complex procedure that scientists haven’t completely figured out yet. Complications may arise from the altering of genes that are not the desired outcome as genes usually have more than one function.
Moral arguments that contest the use of HGE include violations of divine law in some religions and Natural Law which deems it as unnatural and therefore wrong. Another key argument made against HGE is the fear of widening the gap between social classes. The technology would primarily be available to those who could afford it creating social class issues between genetically modified humans and non-genetically modified humans.Another main argument is whether it is justifiable to allocate money to bio technologies when there are other current social issues that would benefit more people rather than the needs of the few privileged individuals. Some have also argued for the need to shift the conversation about HGE towards developing adequate ethical policy to regulate the use of HGE.
Turning the attention away from complete opposition will bring to light more ethically constructive measures for the mechanisms to be used in HGE. Ethical dilemmas of technical developments of human genetic engineering are also prevalent arguing that somatic cell modifications are less likely to harm humans than germline cell modifications.
Molecular biologist Lee M. Silver has posited that unlike Aldous Huxley’s Brave New World, where a totalitarian government employs eugenics to control the genetic makeup within society, the use of gene therapy to design children will be spread through what he calls “free market eugenics” (Silver 315). Wealthy families will opt to design their child with genetic advantages because other families are doing so. Silver believes this use of germline gene therapy will mean wealthy families pass down enhanced traits to their children, potentially disadvantaging poorer families that cannot afford the technology. (Silver 313) However, according to James Hughes, it is possible that Medicaid will cover the costs for fertility services, eliminating the inequality.
Future genetic intervention technologies will allow parents the ability to provide genetic inputs for their children. Hammond (2010) compared the differences between conventional neglect and genetic neglect. Conventional neglect being defined as providing bad environmental inputs, such as a parent failing to feed her child or shaking her child. Genetic neglect being defined as failing to prevent genetic disorders, such as hereditary spastic paraplegia, when a parent has the ability to do so. Hammond stated that parents who could provide adequate genetic input for their children, but fails to do so, is guilty of genetic neglect, which she argued is just as severe as conventional neglect and that we are "morally obliged to use some genetic interventions to prevent some serious genetic disabilities and diseases."
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