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Category Archives: Human Genetic Engineering

Genome editing – Wikipedia

Genome editing, or genome engineering, is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism. Unlike early genetic engineering techniques that randomly inserts genetic material into a host genome, genome editing targets the insertions to site specific locations.

In 2018, the common methods for such editing use engineered nucleases, or "molecular scissors". These nucleases create site-specific double-strand breaks (DSBs) at desired locations in the genome. The induced double-strand breaks are repaired through nonhomologous end-joining (NHEJ) or homologous recombination (HR), resulting in targeted mutations ('edits').

As of 2015 four families of engineered nucleases were used: meganucleases, zinc finger nucleases (ZFNs), transcription activator-like effector-based nucleases (TALEN), and the clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) system.[1][2][3][4] Nine genome editors were available as of 2017.[5]

Genome editing with engineered nucleases, i.e. all three major classes of these enzymeszinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and engineered meganucleaseswere selected by Nature Methods as the 2011 Method of the Year.[6] The CRISPR-Cas system was selected by Science as 2015 Breakthrough of the Year.[7]

Genetic engineering as a method of introducing new genetic elements into organisms has been around since the 1970s. One drawback of this technology has been the random nature with which the DNA is inserted into the hosts genome. This can impair or alter other genes within the organism. Methods were sought which targeted the inserted genes to specific sites within an organism genome. As well as reducing off-target effects it also enabled the editing of specific sequences within a genome. This could be used for research purposes, by targeting mutations to specific genes, and in gene therapy. By inserting a functional gene into an organism and targeting it to replace the defective one it could be possible to cure certain genetic diseases.

Early methods to target genes to certain sites within a genome (called gene targeting) relied on homologous recombination (HR).[8] By creating DNA constructs that contain a template that matches the targeted genome sequence it is possible that the HR processes within the cell will insert the construct at the desired location. Using this method on embryonic stem cells led to the development of transgenic mice with targeted genes knocked out. It has also been possible to knock in genes or alter gene expression patterns.[9] In recognition of their discovery of how homologous recombination can be used to introduce genetic modifications in mice through embryonic stem cells, Mario Capecchi, Martin Evans and Oliver Smithies were awarded the 2007 Nobel Prize for Physiology or Medicine.[10]

If a vital gene is knocked out it can prove lethal to the organism. In order to study the function of these genes site specific recombinases (SSR) were used. The two most common types are the Cre-LoxP and Flp-FRT systems. Cre recombinase is an enzyme that removes DNA by homologous recombination between binding sequences known as Lox-P sites. The Flip-FRT system operates in a similar way, with the Flip recombinase recognising FRT sequences. By crossing an organism containing the recombinase sites flanking the gene of interest with an organism that express the SSR under control of tissue specific promoters, it is possible to knock out or switch on genes only in certain cells. These techniques were also used to remove marker genes from transgenic animals. Further modifications of these systems allowed researchers to induce recombination only under certain conditions, allowing genes to be knocked out or expressed at desired times or stages of development.[9]

Genome editing relies on the concept of DNA double stranded break (DSB) repair mechanics. There are two major pathways that repair DSB; non-homologous end joining (NHEJ) and homology directed repair (HDR). NHEJ uses a variety of enzymes to directly join the DNA ends while the more accurate HDR uses a homologous sequence as a template for regeneration of missing DNA sequences at the break point. This can be exploited by creating a vector with the desired genetic elements within a sequence that is homologous to the flanking sequences of a DSB. This will result in the desired change being inserted at the site of the DSB. While HDR based gene editing is similar to the homologous recombination based gene targeting, the rate of recombination is increased by at least three orders of magnitude.[11]

The key to genome editing is creating a DSB at a specific point within the genome. Commonly used restriction enzymes are effective at cutting DNA, but generally recoginze and cut at multiple sites. To overcome this challenge and create site-specific DSB, three distinct classes of nucleases have been discovered and bioengineered to date. These are the Zinc finger nucleases (ZFNs), transcription-activator like effector nucleases (TALEN), meganucleases and the clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) system.

Meganucleases, discovered in the late 1980s, are enzymes in the endonuclease family which are characterized by their capacity to recognize and cut large DNA sequences (from 14 to 40 base pairs).[12] The most widespread and best known meganucleases are the proteins in the LAGLIDADG family, which owe their name to a conserved amino acid sequence.

Meganucleases, found commonly in microbial species, have the unique property of having very long recognition sequences (>14bp) thus making them naturally very specific.[13][14] However, there is virtually no chance of finding the exact meganuclease required to act on a chosen specific DNA sequence. To overcome this challenge, mutagenesis and high throughput screening methods have been used to create meganuclease variants that recognize unique sequences.[14][15] Others have been able to fuse various meganucleases and create hybrid enzymes that recognize a new sequence.[16][17] Yet others have attempted to alter the DNA interacting aminoacids of the meganuclease to design sequence specific meganucelases in a method named rationally designed meganuclease.[18] Another approach involves using computer models to try to predict as accurately as possible the activity of the modified meganucleases and the specificity of the recognized nucleic sequence.[19]

A large bank containing several tens of thousands of protein units has been created. These units can be combined to obtain chimeric meganucleases that recognize the target site, thereby providing research and development tools that meet a wide range of needs (fundamental research, health, agriculture, industry, energy, etc.) These include the industrial-scale production of two meganucleases able to cleave the human XPC gene; mutations in this gene result in Xeroderma pigmentosum, a severe monogenic disorder that predisposes the patients to skin cancer and burns whenever their skin is exposed to UV rays.[20]

Meganucleases have the benefit of causing less toxicity in cells than methods such as Zinc finger nuclease (ZFN), likely because of more stringent DNA sequence recognition;[14] however, the construction of sequence-specific enzymes for all possible sequences is costly and time consuming, as one is not benefiting from combinatorial possibilities that methods such as ZFNs and TALEN-based fusions utilize.

As opposed to meganucleases, the concept behind ZFNs and TALEN technology is based on a non-specific DNA cutting catalytic domain, which can then be linked to specific DNA sequence recognizing peptides such as zinc fingers and transcription activator-like effectors (TALEs).[21] The first step to this was to find an endonuclease whose DNA recognition site and cleaving site were separate from each other, a situation that is not the most common among restriction enzymes.[21] Once this enzyme was found, its cleaving portion could be separated which would be very non-specific as it would have no recognition ability. This portion could then be linked to sequence recognizing peptides that could lead to very high specificity.

Zinc finger motifs occur in several transcription factors. The zinc ion, found in 8% of all human proteins, plays an important role in the organization of their three-dimensional structure. In transcription factors, it is most often located at the protein-DNA interaction sites, where it stabilizes the motif. The C-terminal part of each finger is responsible for the specific recognition of the DNA sequence.

The recognized sequences are short, made up of around 3 base pairs, but by combining 6 to 8 zinc fingers whose recognition sites have been characterized, it is possible to obtain specific proteins for sequences of around 20 base pairs. It is therefore possible to control the expression of a specific gene. It has been demonstrated that this strategy can be used to promote a process of angiogenesis in animals.[22] It is also possible to fuse a protein constructed in this way with the catalytic domain of an endonuclease in order to induce a targeted DNA break, and therefore to use these proteins as genome engineering tools.[23]

The method generally adopted for this involves associating two DNA binding proteins each containing 3 to 6 specifically chosen zinc fingers with the catalytic domain of the FokI endonuclease which need to dimerize to cleave the double-strand DNA. The two proteins recognize two DNA sequences that are a few nucleotides apart. Linking the two zinc finger proteins to their respective sequences brings the two FokI domains closer together. FokI requires dimerization to have nuclease activity and this means the specificity increases dramatically as each nuclease partner would recognize a unique DNA sequence. To enhance this effect, FokI nucleases have been engineered that can only function as heterodimers.[24]

Several approaches are used to design specific zinc finger nucleases for the chosen sequences. The most widespread involves combining zinc-finger units with known specificities (modular assembly). Various selection techniques, using bacteria, yeast or mammal cells have been developed to identify the combinations that offer the best specificity and the best cell tolerance. Although the direct genome-wide characterization of zinc finger nuclease activity has not been reported, an assay that measures the total number of double-strand DNA breaks in cells found that only one to two such breaks occur above background in cells treated with zinc finger nucleases with a 24 bp composite recognition site and obligate heterodimer FokI nuclease domains.[24]

The heterodimer functioning nucleases would avoid the possibility of unwanted homodimer activity and thus increase specificity of the DSB. Although the nuclease portions of both ZFNs and TALEN constructs have similar properties, the difference between these engineered nucleases is in their DNA recognition peptide. ZFNs rely on Cys2-His2 zinc fingers and TALEN constructs on TALEs. Both of these DNA recognizing peptide domains have the characteristic that they are naturally found in combinations in their proteins. Cys2-His2 Zinc fingers typically happen in repeats that are 3 bp apart and are found in diverse combinations in a variety of nucleic acid interacting proteins such as transcription factors. Each finger of the Zinc finger domain is completely independent and the binding capacity of one finger is impacted by its neighbor. TALEs on the other hand are found in repeats with a one-to-one recognition ratio between the amino acids and the recognized nucleotide pairs. Because both zinc fingers and TALEs happen in repeated patterns, different combinations can be tried to create a wide variety of sequence specificities.[13] Zinc fingers have been more established in these terms and approaches such as modular assembly (where Zinc fingers correlated with a triplet sequence are attached in a row to cover the required sequence), OPEN (low-stringency selection of peptide domains vs. triplet nucleotides followed by high-stringency selections of peptide combination vs. the final target in bacterial systems), and bacterial one-hybrid screening of zinc finger libraries among other methods have been used to make site specific nucleases.

Zinc finger nucleases are research and development tools that have already been used to modify a range of genomes, in particular by the laboratories in the Zinc Finger Consortium. The US company Sangamo BioSciences uses zinc finger nucleases to carry out research into the genetic engineering of stem cells and the modification of immune cells for therapeutic purposes.[25][26] Modified T lymphocytes are currently undergoing phase I clinical trials to treat a type of brain tumor (glioblastoma) and in the fight against AIDS.[24]

Transcription activator-like effector nucleases (TALENs) are specific DNA-binding proteins that feature an array of 33 or 34-amino acid repeats. TALENs are artificial restriction enzymes designed by fusing the DNA cutting domain of a nuclease to TALE domains, which can be tailored to specifically recognize a unique DNA sequence. These fusion proteins serve as readily targetable "DNA scissors" for gene editing applications that enable to perform targeted genome modifications such as sequence insertion, deletion, repair and replacement in living cells.[27] The DNA binding domains, which can be designed to bind any desired DNA sequence, comes from TAL effectors, DNA-binding proteins excreted by plant pathogenic Xanthomanos app. TAL effectors consists of repeated domains, each of which contains a highly considered sequence of 34 amino acids, and recognize a single DNA nucleotide within the target site. The nuclease can create double strand breaks at the target site that can be repaired by error-prone non-homologous end-joining (NHEJ), resulting in gene disruptions through the introduction of small insertions or deletions. Each repeat is conserved, with the exception of the so-called repeat variable di-residues (RVDs) at amino acid positions 12 and 13. The RVDs determine the DNA sequence to which the TALE will bind. This simple one-to-one correspondence between the TALE repeats and the corresponding DNA sequence makes the process of assembling repeat arrays to recognize novel DNA sequences straightforward. These TALENs can be fused to the catalytic domain from a DNA nuclease, FokI, to generate a transcription activator-like effector nuclease (TALEN). The resultant TALEN constructs combine specificity and activity, effectively generating engineered sequence-specific nucleases that bind and cleave DNA sequences only at pre-selected sites. The TALEN target recognition system is based on an easy-to-predict code. TAL nucleases are specific to their target due in part to the length of their 30+ base pairs binding site. TALEN can be performed within a 6 base pairs range of any single nucleotide in the entire genome.[28]

TALEN constructs are used in a similar way to designed zinc finger nucleases, and have three advantages in targeted mutagenesis: (1) DNA binding specificity is higher, (2) off-target effects are lower, and (3) construction of DNA-binding domains is easier.

CRISPRs (Clustered Regularly Interspaced Short Palindromic Repeats) are genetic elements that bacteria use as a kind of acquired immunity to protect against viruses. They consist of short sequences that originate from viral genomes and have been incorporated into the bacterial genome. Cas (CRISPR associated proteins) process these sequences and cut matching viral DNA sequences. By introducing plasmids containing Cas genes and specifically constructed CRISPRs into eukaryotic cells, the eukaryotic genome can be cut at any desired position.[29] Several companies, including Cellectis[30] and Editas, have been working to monetize the CRISPR method while developing gene-specific therapies.[31][32]

Meganucleases method of gene editing is the least efficient of the methods mentioned above. Due to the nature of its DNA-binding element and the cleaving element, it is limited to recognizing one potential target every 1,000 nucleotides.[4] ZFN was developed to overcome the limitations of meganuclease. The number of possible targets ZFN can recognized was increased to one in every 140 nucleotides.[4] However, both methods are unpredictable due to the ability of their DNA-binding elements affecting each other. As a result, high degrees of expertise and lengthy and costly validations processes are required.

TALE nucleases being the most precise and specific method yields a higher efficiency than the previous two methods. It achieves such efficiency because the DNA-binding element consists of an array of TALE subunits, each of them having the capability of recognizing a specific DNA nucleotide chain independent from others, resulting in a higher number of target sites with high precision. New TALE nucleases take about one week and a few hundred dollars to create, with specific expertise in molecular biology and protein engineering.[4]

CRISPR nucleases have a slightly lower precision when compared to the TALE nucleases. This is caused by the need of having a specific nucleotide at one end in order to produce the guide RNA that CRISPR uses to repair the double-strand break it induces. It has been shown to be the quickest and cheapest method, only costing less than two hundred dollars and a few days of time.[4] CRISPR also requires the least amount of expertise in molecular biology as the design lays in the guide RNA instead of the proteins. One major advantage that CRISPR has over the ZFN and TALEN methods is that it can be directed to target different DNA sequences using its ~80nt CRISPR sgRNAs, while both ZFN and TALEN methods required construction and testing of the proteins created for targeting each DNA sequence.[33]

Because off-target activity of an active nuclease would have potentially dangerous consequences at the genetic and organismal levels, the precision of meganucleases, ZFNs, CRISPR, and TALEN-based fusions has been an active area of research. While variable figures have been reported, ZFNs tend to have more cytotoxicity than TALEN methods or RNA-guided nucleases, while TALEN and RNA-guided approaches tend to have the greatest efficiency and fewer off-target effects.[34] Based on the maximum theoretical distance between DNA binding and nuclease activity, TALEN approaches result in the greatest precision.[4]

The methods for scientists and researchers wanting to study genomic diversity and all possible associated phenotypes were very slow, expensive, and inefficient. Prior to this new revolution, researchers would have to do single-gene manipulations and tweak the genome one little section at a time, observe the phenotype, and start the process over with a different single-gene manipulation.[35] Therefore, researchers at the Wyss Institute at Harvard University designed the MAGE, a powerful technology that improves the process of in vivo genome editing. It allows for quick and efficient manipulations of a genome, all happening in a machine small enough to put on top of a small kitchen table. Those mutations combine with the variation that naturally occurs during cell mitosis creating billions of cellular mutations.

Chemically combined, synthetic single-stranded DNA (ssDNA) and a pool of oligionucleotides are introduced at targeted areas of the cell thereby creating genetic modifications. The cyclical process involves transformation of ssDNA (by electroporation) followed by outgrowth, during which bacteriophage homologous recombination proteins mediate annealing of ssDNAs to their genomic targets. Experiments targeting selective phenotypic markers are screened and identified by plating the cells on differential medias. Each cycle ultimately takes 2.5 hours to process, with additional time required to grow isogenic cultures and characterize mutations. By iteratively introducing libraries of mutagenic ssDNAs targeting multiple sites, MAGE can generate combinatorial genetic diversity in a cell population. There can be up to 50 genome edits, from single nucleotide base pairs to whole genome or gene networks simultaneously with results in a matter of days.[35]

MAGE experiments can be divided into three classes, characterized by varying degrees of scale and complexity: (i) many target sites, single genetic mutations; (ii) single target site, many genetic mutations; and (iii) many target sites, many genetic mutations.[35] An example of class three was reflected in 2009, where Church and colleagues were able to program Escherichia coli to produce five times the normal amount of lycopene, an antioxidant normally found in tomato seeds and linked to anti-cancer properties. They applied MAGE to optimize the 1-deoxy-d-xylulose-5-phosphate (DXP) metabolic pathway in Escherichia coli to overproduce isoprenoid lycopene. It took them about 3 days and just over $1,000 in materials. The ease, speed, and cost efficiency in which MAGE can alter genomes can transform how industries approach the manufacturing and production of important compounds in the bioengineering, bioenergy, biomedical engineering, synthetic biology, pharmaceutical, agricultural, and chemical industries.

As of 2012 efficient genome editing had been developed for a wide range of experimental systems ranging from plants to animals, often beyond clinical interest, and was becoming a standard experimental strategy in research labs.[36] The recent generation of rat, zebrafish, maize and tobacco ZFN-mediated mutants and the improvements in TALEN-based approaches testify to the significance of the methods, and the list is expanding rapidly. Genome editing with engineered nucleases will likely contribute to many fields of life sciences from studying gene functions in plants and animals to gene therapy in humans. For instance, the field of synthetic biology which aims to engineer cells and organisms to perform novel functions, is likely to benefit from the ability of engineered nuclease to add or remove genomic elements and therefore create complex systems.[36] In addition, gene functions can be studied using stem cells with engineered nucleases.

Listed below are some specific tasks this method can carry out:

The combination of recent discoveries in genetic engineering, particularly gene editing and the latest improvement in bovine reproduction technologies (e.g. in vitro embryo culture) allows for genome editing directly in fertilised oocytes using synthetic highly specific endonucleases. RNA-guided endonucleases:clustered regularly interspaced short palindromic repeats associated Cas9 (CRISPR/Cas9) are a new tool, further increasing the range of methods available. In particular CRISPR/Cas9 engineered endonucleases allows the use of multiple guide RNAs for simultaneous Knockouts (KO) in one step by cytoplasmic direct injection (CDI) on mammalian zygotes.[37]

Thanks to the parallel development of single cell transcriptomics, genome editing and new stem cell models we are now entering a scientifically exciting period where functional genetics is no longer restricted to animal models but can be performed directly in human samples. Single cell gene expression analysis has resolved a transcriptional road-map of human development from which key candidate genes are being identified for functional studies. Using global transcriptomics data to guide experimentation, the CRISPR based genome editing tool has made it feasible to disrupt or remove key genes in order to elucidate function in a human setting. [38]

Genome editing using Meganuclease,[39] ZFNs, and TALEN provides a new strategy for genetic manipulation in plants and are likely to assist in the engineering of desired plant traits by modifying endogenous genes. For instance, site-specific gene addition in major crop species can be used for 'trait stacking' whereby several desired traits are physically linked to ensure their co-segregation during the breeding processes.[24] Progress in such cases have been recently reported in Arabidopsis thaliana[40][41][42] and Zea mays. In Arabidopsis thaliana, using ZFN-assisted gene targeting, two herbicide-resistant genes (tobacco acetolactate synthase SuRA and SuRB) were introduced to SuR loci with as high as 2% transformed cells with mutations.[43] In Zea mays, disruption of the target locus was achieved by ZFN-induced DSBs and the resulting NHEJ. ZFN was also used to drive herbicide-tolerance gene expression cassette (PAT) into the targeted endogenous locus IPK1 in this case.[44] Such genome modification observed in the regenerated plants has been shown to be inheritable and was transmitted to the next generation.[44] A potentially successful example of the application of genome editing techniques in crop improvement can be found in banana, where scientists used CRISPR/Cas9 editing to inactivate the endogenous banana streak virus in the B genome of banana (Musa spp.) to overcome a major challenge in banana breeding.[45]

In addition, TALEN-based genome engineering has been extensively tested and optimized for use in plants.[46]TALEN fusions have also been used by a U.S. food ingredient company, Calyxt,[47] to improve the quality of soybean oil products[48] and to increase the storage potential of potatoes[49]

Several optimizations need to be made in order to improve editing plant genomes using ZFN-mediated targeting.[50] There is a need for reliable design and subsequent test of the nucleases, the absence of toxicity of the nucleases, the appropriate choice of the plant tissue for targeting, the routes of induction of enzyme activity, the lack of off-target mutagenesis, and a reliable detection of mutated cases.[50]

A common delivery method for CRISPR/Cas9 in plants is Agrobacterium-based transformation.[51] T-DNA is introduced directly into the plant genome by a T4SS mechanism. Cas9 and gRNA-based expression cassettes are turned into Ti plasmids, which are transformed in Agrobacterium for plant application.[51] To improve Cas9 delivery in live plants, viruses are being used more effective transgene delivery.[51]

The ideal gene therapy practice is that which replaces the defective gene with a normal allele at its natural location. This is advantageous over a virally delivered gene as there is no need to include the full coding sequences and regulatory sequences when only a small proportions of the gene needs to be altered as is often the case.[52] The expression of the partially replaced genes is also more consistent with normal cell biology than full genes that are carried by viral vectors.

The first clinical use of TALEN-based genome editing was in the treatment of CD19+ acute lymphoblastic leukemia in an 11-month old child in 2015. Modified donor T cells were engineered to attack the leukemia cells, to be resistant to Alemtuzumab, and to evade detection by the host immune system after introduction.[53][54]

Extensive research has been done in cells and animals using CRISPR-Cas9 to attempt to correct genetic mutations which cause genetic diseases such as Down syndrome, spina bifida, anencephaly, and Turner and Klinefelter syndromes.[55]

In February 2019, medical scientists working with Sangamo Therapeutics, headquartered in Richmond, California, announced the first ever "in body" human gene editing therapy to permanently alter DNA - in a patient with Hunter Syndrome.[56] Clinical trials by Sangamo involving gene editing using Zinc Finger Nuclease (ZFN) are ongoing.[57]

Researchers have used CRISPR-Cas9 gene drives to modify genes associated with sterility in A. gambiae, the vector for malaria.[58] This technique has further implications in eradicating other vector borne diseases such as yellow fever, dengue, and Zika.[59]

The CRISPR-Cas9 system can be programmed to modulate the population of any bacterial species by targeting clinical genotypes or epidemiological isolates. It can selectively enable the beneficial bacterial species over the harmful ones by eliminating pathogen, which gives it an advantage over broad-spectrum antibiotics.[35]

Antiviral applications for therapies targeting human viruses such as HIV, herpes, and hepatitis B virus are under research. CRISPR can be used to target the virus or the host to disrupt genes encoding the virus cell-surface receptor proteins.[33] In November 2018, He Jiankui announced that he had edited two human embryos, to attempt to disable the gene for CCR5, which codes for a receptor that HIV uses to enter cells. He said that twin girls, Lulu and Nana, had been born a few weeks earlier. He said that the girls still carried functional copies of CCR5 along with disabled CCR5 (mosaicism) and were still vulnerable to HIV. The work was widely condemned as unethical, dangerous, and premature.[60]

In January 2019, scientists in China reported the creation of five identical cloned gene-edited monkeys, using the same cloning technique that was used with Zhong Zhong and Hua Hua the first ever cloned monkeys - and Dolly the sheep, and the same gene-editing Crispr-Cas9 technique allegedly used by He Jiankui in creating the first ever gene-modified human babies Lulu and Nana. The monkey clones were made in order to study several medical diseases.[61][62]

In the future, an important goal of research into genome editing with engineered nucleases must be the improvement of the safety and specificity of the nucleases. For example, improving the ability to detect off-target events can improve our ability to learn about ways of preventing them. In addition, zinc-fingers used in ZFNs are seldom completely specific, and some may cause a toxic reaction. However, the toxicity has been reported to be reduced by modifications done on the cleavage domain of the ZFN.[52]

In addition, research by Dana Carroll into modifying the genome with engineered nucleases has shown the need for better understanding of the basic recombination and repair machinery of DNA. In the future, a possible method to identify secondary targets would be to capture broken ends from cells expressing the ZFNs and to sequence the flanking DNA using high-throughput sequencing.[52]

Because of the ease of use and cost-efficiency of CRISPR, extensive research is currently being done on it. There are now more publications on CRISPR than ZFN and TALEN despite how recent the discovery of CRISPR is.[33] Both CRISPR and TALEN are favored to be the choices to be implemented in large-scale productions due to their precision and efficiency.

Genome editing occurs also as a natural process without artificial genetic engineering. The agents that are competent to edit genetic codes are viruses or subviral RNA-agents.

Although GEEN has higher efficiency than many other methods in reverse genetics, it is still not highly efficient; in many cases less than half of the treated populations obtain the desired changes.[43] For example, when one is planning to use the cell's NHEJ to create a mutation, the cell's HDR systems will also be at work correcting the DSB with lower mutational rates.

Traditionally, mice have been the most common choice for researchers as a host of a disease model. CRISPR can help bridge the gap between this model and human clinical trials by creating transgenic disease models in larger animals such as pigs, dogs, and non-human primates.[63][64] Using the CRISPR-Cas9 system, the programmed Cas9 protein and the sgRNA can be directly introduced into fertilized zygotes to achieve the desired gene modifications when creating transgenic models in rodents. This allows bypassing of the usual cell targeting stage in generating transgenic lines, and as a result, it reduces generation time by 90%.[64]

One potential that CRISPR brings with its effectiveness is the application of xenotransplantation. In previous research trials, CRISPR demonstrated the ability to target and eliminate endogenous retroviruses, which reduces the risk of transmitting diseases and reduces immune barriers.[33] Eliminating these problems improves donor organ function, which brings this application closer to a reality.

In plants, genome editing is seen as a viable solution to the conservation of biodiversity. Gene drive are a potential tool to alter the reproductive rate of invasive species, although there are significant associated risks. [65]

Many transhumanists see genome editing as a potential tool for human enhancement.[66][67][68] Australian biologist and Professor of Genetics David Andrew Sinclair notes that "the new technologies with genome editing will allow it to be used on individuals (...) to have (...) healthier children" designer babies.[69] According to a September 2016 report by the Nuffield Council on Bioethics in the future it may be possible to enhance people with genes from other organisms or wholly synthetic genes to for example improve night vision and sense of smell.[70][71]

The American National Academy of Sciences and National Academy of Medicine issued a report in February 2017 giving qualified support to human genome editing.[72] They recommended that clinical trials for genome editing might one day be permitted once answers have been found to safety and efficiency problems "but only for serious conditions under stringent oversight."[73]

In the 2016 Worldwide Threat Assessment of the US Intelligence Community statement United States Director of National Intelligence, James R. Clapper, named genome editing as a potential weapon of mass destruction, stating that genome editing conducted by countries with regulatory or ethical standards "different from Western countries" probably increases the risk of the creation of harmful biological agents or products. According to the statement the broad distribution, low cost, and accelerated pace of development of this technology, its deliberate or unintentional misuse might lead to far-reaching economic and national security implications.[74][75][76] For instance technologies such as CRISPR could be used to make "killer mosquitoes" that cause plagues that wipe out staple crops.[76]

According to a September 2016 report by the Nuffield Council on Bioethics, the simplicity and low cost of tools to edit the genetic code will allow amateurs or "biohackers" to perform their own experiments, posing a potential risk from the release of genetically modified bugs. The review also found that the risks and benefits of modifying a person's genome and having those changes pass on to future generations are so complex that they demand urgent ethical scrutiny. Such modifications might have unintended consequences which could harm not only the child, but also their future children, as the altered gene would be in their sperm or eggs.[70][71] In 2001 Australian researchers Ronald Jackson and Ian Ramshaw were criticized for publishing a paper in the Journal of Virology that explored the potential control of mice, a major pest in Australia, by infecting them with an altered mousepox virus that would cause infertility as the provided sensitive information could lead to the manufacture of biological weapons by potential bioterrorists who might use the knowledge to create vaccine resistant strains of other pox viruses, such as smallpox, that could affect humans.[71][77] Furthermore, there are additional concerns about the ecological risks of releasing gene drives into wild populations.[71][78][79]

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What Can We Expect from Human Genetic Engineering …

Lee Silver,Remaking Eden: Cloning and Beyond in a Brave New World,Avon Books, 1997, 317 pp.

What can we expect from human genetic engineering? How will cloning change our species? Can governments misuse genetic technology? These are some of the questions Lee Silver tries to answer inRemaking Eden.This book is so breezy it reads as if it were pitched to readers ofMademoiselle,but Prof. Silver clearly knows his field and makes no secret of his enthusiasm for using science to improve on nature. Whatever scruplesreligious or otherwiseone may have about the advisability of tinkering with human reproduction, this book leaves little doubt that human cloning and designer babies are likely to be common in the next century.

Just a Small Business

Prof. Silver explains that cloning will be a crucial step in our ability to manipulate reproduction. Last years successful cloning of a sheep means there should be no scientific obstacles to doing the same thing with humans, but what is a clone and how does cloning work? A clone is an exact genetic copy of an organism. Clones are easily produced by plants that can be propagated from cuttings, but animals dont reproduce that way. A clone of a person would be made by putting his genetic material into an embryonic cell, implanting that cell in a womb, and letting it develop to term. Biologically, a clone is no different from an identical twin, except that it is born laterperhaps many years later.

The news of the sheep cloning was met with widespread hostility, and people from President Clinton on down urged that cloning of humans be prohibited. Prof. Silver thinks opposition is both futile (because cloning will be impossible to ban) and misplaced (because cloning will be good and useful). He argues that fancy reproductive genetics cannot be prevented because it does not require large-scale investment, and can be done virtually anywhere. If the United States bans it, Singapore or North Korea or the Cayman Islands will welcome the small businesses that will inevitably spring up to provide it.

According to Prof. Silver, cloning and its associated techniques are good, partly because only individuals, not governments, are likely to use them. There are several reasons for this. First, human cloning starts with a single cell that must be grown into an adult, so it takes 18 to 20 years. Champion athletes or obedient soldiers cannot be cranked out of a clone factory fully-grown, and Prof. Silver suspects that few governments have the patience to wait for clones to grow up. He also reports that in the foreseeable future the chances of creating an artificial womb are slim to none, since the chemical communications between mother and fetus are too complicated to reproduce. Cloning will therefore require human wombs, and large-scale government cloning would require a slave army of young women compelled to produce and rear government-issue babies. This is improbable even under the worst dictators.

Who, then, would clone and why? Since cloning will be labor-intensive, only the rich will be able to afford it. Some peopleand not necessarily egomaniacswill want the nearest thing yet to another chance at life: the opportunity to rear a genetic carbon copy of themselves.

Prof. Silver offers other more exotic possibilities: A couple could go infertile before it had all the children it wanted and could decide to clone the one(s) it already had rather than adopt. A lesbian could decide to clone herself and implant the embryo in her partners wombboth women would then be biological mothers of the resulting child. If the only child of a couple were killed in an accident the parents might decide to clone the child (from its remaining tissue) rather than start over. At a more gruesome level, a clone might be produced because it would be a perfectly compatible organ donor for someone who needed new parts. Some types of useful tissue are already present in the fetus, so the clone could be aborted and all its useful bits harvested.

Cloning makes for startling possibilities. A woman who particularly admired her parents could clone them, have them implanted in her own womb, and rear them. She would then be the birth mother of people who were, genetically, her own parents. Also, since human tissues can be stored indefinitely in the deep freeze, a long-dead ancestors genes could be thawed out and given another try. A child could grow up to learn that what he had always thought was his brother wasgeneticallyhis great-grandfather.

Prof. Silver points out that it is possible to clone someone who has never been born. An aborted fetus has all the genetic material anyone needs for cloning. Spookier still is what could be done with the fact that male and female fetuses already contain eggs and the precursors of sperm. If these were harvested and used for in vitro fertilization, someone could be born of parents who were, themselves, never born. Prof. Silver does not necessarily endorse any of thishe is simply explaining what is now or soon will be possible. And to those who find these ideas repulsive, he points out that when in vitro fertilization was first achieved in 1978 it was denounced as playing God. It is now practiced without controversy in 40 different countries, and by the end of 1994 some 140,000 people had come into the world that way.

He also notes that surrogate motherswomen who rent out their wombscontinue to ply their trade, despite bad publicity. In 1986, Mary Beth Whitehead refused to turn over a contract baby she had agreed to carry for an infertile couple, and the saga of Baby M wore on for months. Since then, states have passed laws governing commercial surrogacy, some banning it outright. Others, like Arkansas, are receptive to reproductive contracts and will enforce them even if the surrogate mother does not want to hand over the baby. Prof. Silver reports that surrogates are now selected with such care that there are no more battles over possession. His point is that a procedure that once provoked an outcry is now quietly flourishing. He predicts that other reproductive techniques that now seem outlandish will also gain wide acceptance.

Whatever happens, this will be sport for the rich: In vitro fertilization costs anywhere from $50,000 to $200,000 and the total costs of hiring a stranger to carry your child run to about $50,000.

Improving on Nature

Even more troubling for some people is the prospect of human genetic improvement, but simple techniques of this sort are already being used. If parents use amniocentesis to test an unborn child for genetic diseases, they have the option of aborting the fetus rather than have a baby with a serious defect. This is crude, all-or-nothing selection but it is still a refusal to leave reproduction to chance. Embryo selection is similar but more complex. When infertile couples resort to in vitro fertilization, they usually fertilize several eggs at once to make sure at least one will be usable. If several embryos are left to develop they can be examined and the most promising chosen for implantation. Soon it will be possible to change the genetic contents of the embryo so as to eliminate hereditary diseases and even add desirable qualities.

Prof. Silver notes that cloning will be central to this process because at the pre-implantation stage that will make it possible to work with batches of embryos rather than just one. Biological procedures are never 100 percent reliable, so reproductive genetics needs the margin for error that comes with genetically identical copies. A technician who would never attempt an uncertain maneuver on a single, laboriously-harvested, fertilized, and partially-developed embryo could try it confidently on 100 identical embryos.

Needless to say, there is much controversy about all this. Some people would view the 99 failed-and-discarded embryos as 99 abortions. Likewise, there are doubts about the advisability of tinkering with genetic characteristics that could be passed on to succeeding generations. Indeed, some of the probable methods do seem strange. For example, it should soon be possible to modify the precursor cells that produce human sperm. Harmful characteristics could be eliminated and helpful ones added. These cells could then be implanted into the testes of a pig or mouse, which would produce improvedhuman sperm,which could be harvested and used for in vitro fertilization.

Whatever techniques are used, Prof. Silver suggests that in 100 years or so, true designer babies will be possible. A couple could select their own most desirable traits and add nice features from other people and evenother species.There is no theoretical obstacle to stitching into humans the genes that give dogs a keen sense of smell or even those that permit echolocation in bats or dolphins. Humans may some day be able to see radio waves and infrared light, or even perform photosynthesis.

Prof. Silver recognizes that the children of people who can afford these techniques will dominate society. Every parent with enough money could have beautiful, talented, genius children. Prof. Silver even recognizes that these improved humans could quickly become a distinct species, or even several distinct species, depending on the set of characteristics they selected. Is this eugenics? Indeed it is, says Prof. Silver, who argues that even if the Nazis gave it a bad name, it would be irresponsible not to take control of our genetic destiny now that we are able.

Fantastic as all of this may sound, Prof. Silver is probably at his most convincing when he argues that unless the United States or some other superpower launches a global effort to prevent anyone anywhere from perfecting and practicing these techniques, reproductive engineering will surely come to pass. Parents want the best for their children, and with or without their governments permission they will find a way to get it. Although there will not be new, improved human super-species in our lifetime, Prof. Silver argues that there is no harm in getting used to the idea now.

Original Article

Topics: Book Review, Classics, Eugenics and Dysgenics, Fertility, Science and Genetics

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What Can We Expect from Human Genetic Engineering ...

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Human Genetic Engineering – Evolution 21st Century Style?

So Whats with the Transhumanism Thing?

Transhumanism is a philosophical movement that is strongly related to humanism. It has specific beliefs about what the fate of humanity should be and how technology will help us shape and achieve that future. Ive put together a small number of core topic articles to get you orientated to the transhumanism movement and some of the most important concepts. You can tackle them in any order you want to, but I suggest you do them in this order.

First, have a look at What is transhumanism?, which I think most people would agree is a good place to start.

Right after that one, its a good idea to read Common misconceptions about transhumanists.

If you get those out of the way, you may be interested to read Understanding transhuman rights, which will give you a great idea of what it would be like living in a transhuman society.

Finally, the last two core topics are about concepts that are not subscribed to by all transhumanists, but are so popular in the movement that they deserve to be put here. The first is an article titled What is the singularity and the second is titled What are post-scarcity economics?.

If you get through all the core topics, youll know pretty much all you need in order to feel grounded in this interesting philosophical movement.With that out of the way, let me explain how the rest of the site works.

Transhumanism covers a wide range of ideas, fields, and technologies. So to make it all easier Ive tried to narrow them down to a few key areas. Obviously, many of these technologies overlap with each other, but wherever possible Ive tried to sort them neatly.

There are eight topic sections on this site besides the core topics weve already talked about, so lets look at each of these sections in alphabetical order.

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Human Genetic Engineering - Evolution 21st Century Style?

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Human Genetic Engineering | Free Essays – PhDessay.com

I will be discussing the controversial topic of human genetic engineering and its pros and cons from a biological and social point of view while also trying to answer the question Should human genetic engineering be legal. Genes control health and disease, as well as human traits and behavior. Researchers are Just beginning to use genetic technology to unravel the secrets to these phenotypes (observable trait caused by a gene).

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They are also discovering a range of other potential applications for this technology.

For instance, ongoing advances make it more and more likely that scientists will soon be able to genetically engineer humans to have certain desired traits (this is already done on mice). Of course, the possibility of human genetic engineering raises a number of ethical and legal questions, although such questions almost never have a clear and straight forward answer. The research of bioethics, sociologists, anthropologists, and other social scientists can tell us about how different citizens, cultures, and religions view the moral boundaries or the uses of human genetic engineering.

If human genetic modification Is fully legalized It will be done on the early, early stages of reproduction: from when It Is Just a sperm and an egg to the fetus stage, maybe a slight amount later. At this point of time It Is only legal to perform two types of advance reproductive technologies on humans. The first Is foretelling the egg with sperm In a test tube. This is used to determine the sex and what genes the baby will have, therefore knowing if using a different sperm/egg will be a better choice since one of the genes n the first tested set might be a genetic disease or the parents might prefer a different sex.

The second technique is much like the first. Embryos for a genetic disease; only selected embryos are implanted back into the mothers womb. This is called Pre-implantation Genetic Diagnosis. Now I will discuss what good can come of legalizing human genetic engineering. Really the most useful application of human genetic engineering is preventing hereditary diseases, disabilities and defects/doodlers. Examples include: Down syndrome, Diabetes, color blindness and even allergies.

Stopping these diseases/doodlers before the baby Is even born can help prevent a lot of Issues from happening In the childs future and can possibly save lives. Eventually the disease/disorder will die out because the gene has been removed from the generations making it unable to be passed down. Another application could involve stimulating muscle growth/brain development in turn making the child more athletic or more brainy also changing your childs physical features and traits, such as eye color and hair color.

Now for the bad: Although changing your childs physical traits, deciding to make them more muscular or more smart can seem like a good thing to a some people it is also viewed as a bad thing to some people. Things like a perfect race could arise from these problems, or baby trends, where it Is trendier that year for your kids to have blonde hair then It Is for them to have black or blue eyes rather than green. This Is generally the topic that Is the most talked amongst the public when discussing human genetic engineering.

Other social Issues can be raised such as It Is against gods will, countries creating super human soldiers, countries becoming more like the class system e: people who run business, there is also the issue of the child not having the choice to be genetically modified, the individuality of humans and coasts of genetically modifying also comes into play, such as, can only the rich afford it? From a biological point of view genetic modification could eventually make some genes extinct in a way, where they are no longer needed/deemed useless or maybe they go out of fashion.

In my opinion, I think that genetic modification in humans should be legal, but should only be used for hereditary diseases, disabilities and disorders which help the child but things like letting the parent chose the childs traits do not help the child and he/she also loses their individuality. Also there is the fact that the child doesnt have a choice at what the parents will make them look like. Changing the traits of a child through genetic engineering does not benefit the child and only pleases the parents. In

Conclusion to this essay, there is a high chance that human genetic engineering will be available soon and when it does it will be a very controversial issue, both on a biological and a social point of view. Most social issues come from a negative stand point and are mainly on the regulation of it (coasts, who can use it, what countries can do with it). There is no straight forward answer to the question of should human genetic modification be legal. Although there is a large amount of health benefits, the negative social issues may outweigh them. Word Count: 839

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Most Americans Accept Genetic Engineering of Animals That …

As Americans consider the possible uses of genetic engineering in animals, their reactions are neither uniformly accepting nor resistant; instead, public reactions vary depending on the mechanism and intended purpose of the technology, particularly the extent to which it would bring health benefits to humans.

Presented with five different scenarios of animal genetic engineering that are currently available, in development or considered possible in the future, Americans provide majority support only for the two that have clear potential to pre-empt or ameliorate human illness.

The surveys most widely accepted use of genetic intervention of animals involves mosquitoes. Seven-in-ten Americans (70%) believe that genetically engineering mosquitoes to prevent their reproduction and therefore the spread of some mosquito-borne diseases would be an appropriate use of technology, while about three-in-ten (29%) see the use of genetic engineering for this purpose as taking technology too far.

And a 57% majority considers it appropriate to genetically engineer animals to grow organs or tissues that could be used for humans needing a transplant.

But other uses of animal biotechnology are less acceptable to the public, including the creation of more nutritious meat for human consumption (43% say this is appropriate) or restoring an extinct animal species from a closely related species (32% say this is appropriate). And one application that is already commercially available is largely met with resistance: Just 21% of Americans consider it an appropriate use of technology to genetically engineer aquarium fish to glow using a fluorescence gene, while 77% say this is taking technology too far.

These are some of the findings from a new Pew Research Center survey, conducted April 23-May 6 among a nationally representative sample of 2,537 U.S. adults that looks at public views about genetic engineering of animals a term that encompasses a range of biotechnologies that can add, delete or change an animals existing genetic material and thereby introduce new traits or characteristics.

Although most Americans are largely in agreement that using genetic engineering in mosquitoes to prevent the spread of mosquito-borne illnesses is appropriate, views about other uses of genetic engineering of animals considered in the survey differ by gender, levels of science knowledge andreligiosity. Men are more accepting of these uses of technology than women, those with high science knowledge are more accepting than those with medium or low science knowledge and those low in religious commitment are more accepting than those with medium or high levels of religious commitment.

For example, about two-thirds of men (65%) see genetic engineering of animals to grow human organs or tissues for transplants as appropriate, compared with about half of women (49%). Also, Americans with high science knowledge (72%) are more inclined than those with medium (55%) or low (47%) science knowledge to say this would be appropriate. And a larger share of those with low religious commitment (68%) than medium (54%) or high (48%) religious commitment consider genetic engineering of animals to grow human organs or tissues for transplants to be appropriate.

Emerging developments in animal biotechnology raise new social, ethical and policy issues for society, including the potential impact on animal welfare.

The survey finds that the 52% of Americans who in general oppose the use of animals in scientific research are, perhaps not surprisingly, also more inclined to consider specific uses of genetic engineering of animals to be taking technology too far.

There are large differences between these groups when it comes to using animal biotechnology for humans needing an organ or tissue transplant and the idea of using such technology to produce more nutritious meat.

To better understand peoples beliefs about genetic engineering of animals, the survey asked a subset of respondents to explain, in their own words, the main reason behind their view that genetic engineering in each of these circumstances would be taking technology too far.

A common refrain in these responses raised the possibility of unknown risks for animals, humans or the ecosystem. Some saw these technologies as humankind inappropriately interfering with the natural world or raised general concerns about unknown risks.

About three-in-ten of those who said genetic engineering of mosquitoes would be taking technology too far explained that humankind would be disrupting nature (23%) or interfering with Gods plan (8%).

One respondent put it this way:

Nature is a balance and every time man interferes with it, it doesnt turn out well.

Some 24% of those with objections to the idea of reducing the fertility of mosquitoes through genetic engineering in order to reduce mosquito-borne illnesses raised concerns about the possible impact on the ecosystem.

Such responses include:

I do not think we know enough about the effects of removing a whole class of insectsfrom the environment. What would be the effects on those animal and plants up the chain?

Mosquitoes are part of a complex ecosystem and food chain. By preventing their reproduction, we risk disrupting the entire ecosystem.

Objections to the idea of using animal biotechnology to grow organs or tissues for transplant in humans focused on beliefs about using animals for human benefit (21%) and potential risks for human health from creating human organs from animals (16%).

For example:

In manufacturing organs, the existence of these animals would be miserable in order to cultivate such organs the animals would need to be in a lab setting and would more than likely never see the light of day. I cant ethically say that I would agree with such a practice.

When you mix human and nonhuman genetics I believe that will cause extreme problems down the road.

Animal organs are not made for humans even though some animal and human organs may be very similar. Who knows what side effects this could cause? Even human-to-human organ transplants often reject, so I can only imagine the bad side effects that an animal-to-human transplant would cause. Keep things simple and the way nature intended.

Genetic engineering could produce more nutritious meat by altering animal proteins. Those who think this is taking technology too far raised a number of different concerns. Some cited general concerns about as-yet-unknown risks (20% of those asked), while a similar share (19%) saw this as messing with nature or Gods plan in a way that goes beyond what humans should do.

One respondent put it this way:

Should we as human beings change the course of natures natural selection and potentially introduce unintended serious consequences?

About one-in-ten (12%) objected to the idea on the grounds that people should rely less on meat in their diet or that any genetic engineering in foods is a likely health risk.

One example of these concerns:

Meat is nutritious as it is. There is no need to try to increase nutrition. Rather we should be decreasing human reliance on meat as a foodstuff.

Those who objected to the idea of bringing back extinct species often raised concerns about unintended harm to the ecosystem. Roughly two-in-ten (18%) of those asked explained their views by saying there is a reason that these animals are currently extinct, with some saying these animals would be unlikely to survive if brought back, and another 12% of this group raised potential risks to other species and the ecosystem from bringing an extinct animal into a different world.

For example:

Beware of unintended consequences. The universe is in balance with them extinct. Consider the problems man has created by reintroducing species that have become extinct [in] a given area, i.e., wolves and mountain lions to areas now occupied by humans and domestic livestock.

Others discussed these ideas in terms of Gods plan and human interference with the natural world (23%).

A few examples:

God is the creator of all living things, not mankind. Extinction is part of evolution of the universe.

Nature has selected species to become extinct over millions and millions of years. We have no right to bring animals back and play God.

And 14% said they regard bringing back an extinct species as taking technology too far because they do not see a need or purpose to this, especially as it does not seem to bring any benefit to humans, or that resources should be focused elsewhere.

A sampling of these concerns:

For what purpose would it be done? Is there a benefit to humanity other than having a rare zoo specimen? Would the extinct species cease to become extinct through natural reproduction if not that, the whole effort is without merit.

I dont see the purpose of bringing any animal back. Would it provide a better way of life for humans?

Objections to the idea of changing the appearance of aquarium fish using genetic engineering to make the fish glow often focused on the lack of apparent need or benefit to either humans or animals.

About half (48%) of those who say engineering a glowing fish takes technology too far said they do not see the purpose for humans or society, questioned its necessity or considered it frivolous or a waste of resources.

Some examples:

[While] changing a fish to glow might sound like something people would want to see its not something beneficial to humankind. At this point it would just [be] playing God to entertain rather [than] help us.

Its frivolous. Technology should be used to help people, animals and the environment, not put on a glow show.

Why? If you only do something because you can is not a good reason. If any genetic engineering is allowed it will get out of hand. It would be a fine line that I am sure we would cross.

It seems a frivolous thing to do, much like someone getting plastic surgery to remove wrinkles or other signs of aging. The persons life is not extended by a better appearance. The aquarium fish also do not benefit from their changed appearance.

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Is human genetic engineering ethical? | Debate.org

As students of a high school summer genetic engineering course, we have decided that human genetic engineering is immoral for the following reasons: It would eliminate talent; as stated in The Incredibles, If everyones super, then no one will be. And Playing God is a dangerous game that inevitably ends with a monster.- AnonymousEveryone will be the same, parents will want the perfect child, therefore, everyone will have the same talents and advantages, so it will not make a big difference in society. If a group of people begins to make superior changes in their offspring, the rest of the population will be left with inferior children unless they too join in the practice of designing their baby. Therefore, the company that produces these changes will be in control of the population.If human genetic engineering were to happen, the various figures of god, which millions of people around the world rely on every day would collapse and becomes us, therefore, reducing faith by having us play the role of a god-like figure. While creating the perfect immune system, only diseases that are already known will be prevented. When a new disease comes along, our immune system will not be comparatively as strong. We came to the opinion that genetically engineering designer babies is wrong because the social-economic divide would become increasingly more noticeable and potentially more hostile.Genetically engineering a privileged embryo to be immune to all known diseases would cause the downfall of the pharmaceutics industry, and consequently the deaths of a great number of underprivileged citizens.

When we try to engineer a child, for that is what an embryo is, a child, we change God's plan for the child. If that child was meant to be born with dyslexia, and you take it from them, not only are we taking away something that they will grow through, but we ourselves are playing god. A parent raises a child with unconditional love. If that child is chosen to be a certain sex, hair color, eye color, IQ and all imperfections have been taken out, how can the love of their parents ever be unconditional?

It is meddling with something beyond our grasp, we are not meant to play God and try to create life in the way we wish it to be. We are all formed in our mothers womb just as he wants us to be. "Ps 139:13 - For thou hast possessed my reins: thou hast covered me in my mother's womb." "Isaiah 44:24 - Thus saith the LORD, thy redeemer, and he that formed thee from the womb, I am the LORD that maketh all things; that stretcheth forth the heavens alone; that spreadeth abroad the earth by myself."

I believe it is unethical because it goes against the Bible. I believe that only God can truly affect the genetics of a human being and the science doesn't stand a chance. It is morally wrong and takes God out of it. After all we are talking about a human life here. No matter what people say, the cells science messes with are human beings.

In the bible it says that we were created in gods image. If we genetic engineer on some one then we are tarnishing the image of God. In the move Gattaca they show that only people of higher class and are modified can be great, but look at steven hawking. Steven hawking has helped contrubute so much and look at his diabilaties.

When will we learn the simple fact that everything man has tried to improve on relating to mother nature and creation has ultimately ended up being a step in the wrong direction? Sometimes irreversible changes we could not have forseen show up decades later. When you put something on this earth that never has and never was intended to be here, you can't possibly see the repercussions it will bring about. There is so much we will never understand about the human body, mind and soul. It is foolish and arrogant to think we can experiment with the human race on this level and say we understand it all. When will we learn? We are not God. If you don't believe in the God who created everything, then most likely you will think man is smart enough and powerful enough to cure any disease, engineer life to last indefinitely, and anything else our heart desires, without any consequences. I'm all for advances in healthcare, but we can't possibly think we can improve on what God created can we? In his ultimate wisdom he created the human race, and the universe. Let's just figure out how to build a car that will last more than 10 years before we start engineering the perfect human race. What do you say?

It leaves people to decide what the "ultimate race" would be like. Genetic engineering doesn't cure diseases as people claim. Genetics in one of the most misunderstood realms of science. (Not that I understand it, but the leading scientist can't come to consensus either.) It is used for growth hormone, insulin production, fertility drugs, and vaccines. Since genetics is so risky and these risks are not fully understood, GE on humans should be restricted to research and experimentation in life or death situations.

Why spend money on creating your own child from chosen traits? Let mother nature take its course. Okay? So people... Dont customize your own child, thats just wrong. It may seem appealing at first because you want your child to be so-called perfect, but hey, no one's perfect. Okay?

In the 21st century, we have seen the vast differences in technological advancements in the developed and developing countries in the world. The poor citizens of developing countries generally have less sophisticated technological gadgets compared to those that are wealthier. If we were to allow genetic engineering, it will certainly create an even larger inequality between the rich and the poor. The affluent ones can simply pay to get muscle enhancements or increase their IQ genetically. However, the poor ones will have to toll and work very hard simply to match up to their rich counterparts. This would certainly create an unbalanced society where the rich will continue to advance and become richer whereas the poor will be left behind in this fast-paced race. Thus, this clear distinction between the two groups: the Genetically Modified and the normal being is known as the Genetic Divide. In such a society, the poor will be extremely disadvantaged and it will be even harder to adopt a meritocratic system. Thus, an equal starting platform will no longer exist. Therefore, genetic engineering should not be pursued as it has the potential to cause an unwanted genetic divide in the society.

Though there are many naysayers out there God does exist. He has more power and love than we could possibly imagine. He has a divine plan for every person and tragedy happens for a reason, the ripple effect is endless even if we are too stubborn to see. We do not have the right to play God. If diseases happen they happen for a reason and though tragic there is always something good that comes out of it. Plus, messing with genetics and increasing lifespans in an unnatural way only contributes to overpopulation that much more.

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