Can we edit genes before a baby is born?
Gene therapy
As early in the history of biotechnology as 1990, there have been scientists opposed to attempts to modify the human germline using these new tools, and such concerns have continued as technology progressed. With the advent of new techniques like CRISPR, in March 2015 a group of scientists urged a worldwide moratorium on clinical use of gene editing technologies to edit the human genome in a way that can be inherited. In April 2015, researchers sparked controversy when they reported results of basic research to edit the DNA of non-viable human embryos using CRISPR. A committee of the American National Academy of Sciences and National Academy of Medicine gave qualified support to human genome editing in 2017 once answers have been found to safety and efficiency problems "but only for serious conditions under stringent oversight."
Epigenome editing
Comparing genome-wide epigenetic maps with gene expression has allowed researchers to assign either activating or repressing roles to specific modifications. The importance of DNA sequence in regulating the epigenome has been demonstrated by using DNA motifs to predict epigenomic modification. Further insights into mechanisms behind epigenetics have come from in vitro biochemical and structural analyses. Using model organisms, researchers have been able to describe the role of many chromatin factors through knockout studies. However knocking out an entire chromatin modifier has massive effects on the entire genome, which may not be an accurate representation of its function in a specific context. As one example of this, DNA methylation occurs at repeat regions, promoters, enhancers, and gene bodies. Although DNA methylation at gene promoters typically correlates with gene repression, methylation at gene bodies is correlated with gene activation, and DNA methylation may also play a role in gene splicing. The ability to directly target and edit individual methylation sites is critical to determining the exact function of DNA methylation at a specific site. Epigenome editing is a powerful tool that allows this type of analysis. For site-specific DNA methylation editing as well as for histone editing, genome editing systems have been adapted into epigene editing systems. In short, genome homing proteins with engineered or naturally occurring nuclease functions for gene editing, can be mutated and adapted into purely delivery systems. An epigenetic modifying enzyme or domain can be fused to the homing protein and local epigenetic modifications can be altered upon protein recruitment.
Genome editing
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 amateursor "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 genomeand having those changes pass on to future generationsare 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. 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. Furthermore, there are additional concerns about the ecological risks of releasing gene drives into wild populations.
Eugenics
Societal and political consequences of eugenics call for a place in the discussion on the ethics behind the eugenics movement. Many of the ethical concerns regarding eugenics arise from its controversial past, prompting a discussion on what place, if any, it should have in the future. Advances in science have changed eugenics. In the past, eugenics had more to do with sterilization and enforced reproduction laws. Now, in the age of a progressively mapped genome, embryos can be tested for susceptibility to disease, gender, and genetic defects, and alternative methods of reproduction such as in vitro fertilization are becoming more common. Therefore, eugenics is no longer "ex post facto" regulation of the living but instead preemptive action on the unborn.
Genetic pollution
Not all genetically engineered organisms cause genetic pollution. Genetic engineering has a variety of uses and is specifically defined as a direct manipulation of the genome of an organism. Genetic pollution can occur in response to the introduction of a species that is not native to a particular environment, and genetically engineered organisms are examples of individuals that could cause genetic pollution following introduction. Due to these risks, studies have been done in order to assess the risks of genetic pollution associated with organisms that have been genetically engineered:Not only are there risks in terms of genetic engineering, but there are risks that emerge from species hybridization In Czechoslovakia, ibex were introduced from Turkey and Sinai to help promote the ibex population there, which caused hybrids that produced offspring too early, which caused the overall population to disappear completely. The genes of each population of the ibex in Turkey and Sinai were locally adapted to their environments so when placed in a new environmental context did not flourish. Additionally, the environmental toll that may arise from the introduction of a new species may be so disruptive that the ecosystem is no longer able to sustain certain populations.
Human variability
The concept that nutrition and diet affect phenotype extends to what the mother eats during pregnancy, which can have drastic effects on the outcome of the phenotype of the child. A recent study by researchers at the MRC International Nutrition Group shows that "methylation machinery can be disrupted by nutrient deficiencies and that this can lead to disease" susceptibility in newborn babies. The reason for this is because methyl groups have the ability to silence certain genes. Increased deficiencies of various nutrients such as this have the potential to permanently change the epigenetics of the baby.
Human germline engineering
One of the main arguments against human germline engineering lies in the ethical feeling that it will dehumanize children. At an extreme, parents may be able to completely design their own child, and there is a fear that this will transform children into objects, rather than human beings. There is also a large opposition as people state that by engineering the human germline, there is an attempt at "playing God", and there is a strong opposition to this. One final, and very possible issue that causes a strong opposition of this technology is one that lies within the scientific community itself. Inevitably, this technology would be used for enhancements to the genome, which would likely cause many more to use these same enhancements. By doing this, the genetic diversity of the human race and the human gene pool as we know it would slowly and surely diminish. Despite the controversy surrounding the topic of human germline engineering, it is slowly and very carefully making its way into many labs around the world. These experiments are highly regulated, and they do not include the use of viable human embryos, which allows scientists to refine the techniques, without posing a threat to any real human beings.
Mutation
Mutation can result in many different types of change in sequences. Mutations in genes can either have no effect, alter the product of a gene, or prevent the gene from functioning properly or completely. Mutations can also occur in nongenic regions. One study on genetic variations between different species of "Drosophila" suggests that, if a mutation changes a protein produced by a gene, the result is likely to be harmful, with an estimated 70 percent of amino acid polymorphisms that have damaging effects, and the remainder being either neutral or marginally beneficial. Due to the damaging effects that mutations can have on genes, organisms have mechanisms such as DNA repair to prevent or correct mutations by reverting the mutated sequence back to its original state.
Human germline engineering
In November 2018, researcher Jiankui He claimed that he had created the first human genetically edited babies, known by their pseudonyms, Lulu () and Nana ().{
Michael W. Deem
Deem was an advisor to Jiankui He, who announced in November 2018 that that he had generated the world's first genome-edited babies; Deem was involved in He's research, and was present when people involved in He's study gave consent. Deem came under investigation by Rice after news of the work was made public.
Off-target genome editing
Engineered gene drives using CRISPR-cas9 are currently being tested and have been proposed as strategies to eliminate invasive species and disease vectors. By genetically modifying an organism to express an endogenous sequence-specific endonuclease, a target (such as a fertility gene) can be cleaved on the opposite chromosome. A DSB at the target leads to homologous repair which effectively renders the organism homozygous for the desired target sequence. This strategy, known as a homing drive, can suppress a population by affecting a critical gene or inducing recessive sterility. However, if such a system were released into the wild, the CRISPR-cas9 system would remain function indefinitely. With every subsequent generation, off-target mutations would become increasingly likely and the effects of these mutations on a species would be stochastic. Off-target mutations could disable the suppressive qualities of a gene drive while maintaining the endonuclease expression. In such a situation there would be an increased risk of gene flow between the target species and other species likely leading to undesired outcomes.
Germline mutation
Different germline mutations can affect an individual differently depending on the rest of their genome. A dominant mutation only requires 1 mutated gene to produce the disease phenotype, while a recessive mutation requires both alleles to be mutated to produce the disease phenotype. For example, if the embryo inherits an already mutated allele from the father, and the same allele from the mother underwent an endogenous mutation, then the child will display the disease related to that mutated gene, even though only 1 parent carries the mutant allele. This is only one example of how a child can display a recessive disease while a mutant gene is only carried by one parent. Detection of chromosomal abnormalities can be found in utero for certain diseases by means of blood samples or ultrasound, as well as invasive procedures such as an amniocentesis. Later detection can be found by genome screening.
Sex-limited genes
Epigenetics is the inheritance of additional marks to the genome without changes in its sequence. These factors epigenetic factors may also be sex-limited. Genomic imprinting for example, silencing of one parental allele by DNA methylation, for which sex-limited imprinting has been proposed to resolve intralocus conflict. Genomic imprinting has been shown to be indistinguishable from non-imprinted systems at the population level in some cases, having equivalent evolutionary models. However, this does not hold for sex-limited models of sex-limited imprinting which behave differently depending on which sex imprinting occurs and the parental sex of imprinted allele. Specifically, this affects whether alleles are imprinted in consecutive generations with different evolutionary trajectories (under the same selection fitnesses) arising purely due to sex-limited epigenetics. Thus sex-limited epigenetic traits may have played a pivotal role in the evolution of mammals and other species, particularly as a mechanism to ameliorate intralocus conflict between the sexes.
Horizon Discovery
Gene editing is the process by which specific changes are made to the sequence of a gene within the context of a host cell. By editing the code of a patient-derived cell to introduce or repair a genetic change believed to drive disease, a patient’s disease can be reproduced in a laboratory setting, letting researchers ask important biological questions of potential drugs or cell therapies earlier in the drug discovery process.
Epigenetic regulation of transposable elements in the plant kingdom
Very little is known about the initiation of epigenetic silencing of transposable elements, and aside from the rare exception to this rule, as in the gene Muk, present as an initiator of regulatory epigenetic modification in maize, there are many other unclear aspects of how transposons are regulated in plant genomes. Might they be a first step in evolution that we never knew about? [1] Might they be, simply, a kink in the chain of genetic coding, one that will eventually be worked out? Again, given the lack of information it is hard to say. Future research into this field will see the changing of our conceptions of transposons and their role in eukaryote development, one way or another.
Genome editing
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.
Genetic engineering
Genetic engineering has applications in medicine, research, industry and agriculture and can be used on a wide range of plants, animals and micro organisms. Bacteria, the first organisms to be genetically modified, can have plasmid DNA inserted containing new genes that code for medicines or enzymes that process food and other substrates. Plants have been modified for insect protection, herbicide resistance, virus resistance, enhanced nutrition, tolerance to environmental pressures and the production of edible vaccines. Most commercialised GMOs are insect resistant or herbicide tolerant crop plants. Genetically modified animals have been used for research, model animals and the production of agricultural or pharmaceutical products. The genetically modified animals include animals with genes knocked out, increased susceptibility to disease, hormones for extra growth and the ability to express proteins in their milk.
Genetically modified food
Human-directed genetic manipulation of food began with the domestication of plants and animals through artificial selection at about 10,500 to 10,100 BC. The process of selective breeding, in which organisms with desired traits (and thus with the desired genes) are used to breed the next generation and organisms lacking the trait are not bred, is a precursor to the modern concept of genetic modification (GM). With the discovery of DNA in the early 1900s and various advancements in genetic techniques through the 1970s it became possible to directly alter the DNA and genes within food.
David Baltimore
Baltimore recently joined with other scientists to call for a worldwide moratorium on use of a new genome-editing technique to alter inheritable human DNA. A key step enabling researchers to slice up any DNA sequence they choose was developed by Emmanuelle Charpentier, then at Umea University in Sweden, and Jennifer A. Doudna of the University of California, Berkeley. Reminiscent of the Asilomar conference on recombinant DNA in 1975, those involved want both scientists and the public to be more aware of the ethical issues and risks involved with new techniques for genome modification.
Microsatellite
Length changes of microsatellites within promoters and other cis-regulatory regions can change gene expression quickly, between generations. The human genome contains many (>16,000) short sequence repeats in regulatory regions, which provide ‘tuning knobs’ on the expression of many genes.
Genetic pollution
Genetically engineered organisms are genetically modified in a laboratory, and therefore distinct from those that were bred through artificial selection. In the fields of agriculture, agroforestry and animal husbandry, "genetic pollution" is being used to describe gene flows between GE species and wild relatives.
An early use of the term ""genetic pollution"" in this later sense appears in a wide-ranging review of the potential ecological effects of genetic engineering in The Ecologist magazine in July 1989. It was also popularized by environmentalist Jeremy Rifkin in his 1998 book "The Biotech Century". While intentional crossbreeding between two genetically distinct varieties is described as hybridization with the subsequent introgression of genes, Rifkin, who had played a leading role in the ethical debate for over a decade before, used genetic pollution to describe what he considered to be problems that might occur due the unintentional process of (modernly) genetically modified organisms (GMOs) dispersing their genes into the natural environment by breeding with wild plants or animals.
Elective genetic and genomic testing
Prenatal testing is diagnostic testing of a fetus before birth to detect abnormalities in the chromosomes or genes. Samples for this testing are obtained through invasive procedures such as amniocentesis or chorionic villus sampling. Prenatal testing is different from prenatal screening.
Sex selection
Prior to fertilization with IVF, the fertilized eggs can be genetically biopsied with preimplantation genetic diagnosis (PGD) to increase fertilization success. Once an embryo grows to a 6-8 cell size, a small laser incision in the egg membrane (zona pellucida) allows safe removal of one of the cells. Every cell in the embryo contains an identical copy of the genome of the entire person. Removal of one of these cells does not harm the developing embryo. A Geneticist then studies the chromosomes in the extracted cells for genetic defects and for a definite analysis of the embryo’s gender. Embryos of the desired sex and with acceptable genetics are then placed back into the mother.
Epigenome editing
Editing of gene enhancer regions in the genome through targeted epigenetic modification has been demonstrated by Mendenhall et al. (2013). This study utilized a TALE-LSD1 effector fusion protein in order to target enhancers of genes, to induce enhancer silencing in order to deduce enhancer activity and gene control. Targeting specific enhancers followed by locus specific RT-qPCR allows for the genes affected by the silenced enhancer to be determined. Alternatively, inducing enhancer silencing in regions upstream of genes allows for gene expression to be altered. RT-qPCR can then be utilized to study effects of this on gene expression. This allows for enhancer function and activity to be studied in detail.
Transhumanism
Transhumanists and other supporters of human genetic engineering do not dismiss practical concerns out of hand, insofar as there is a high degree of uncertainty about the timelines and likely outcomes of genetic modification experiments in humans. However, bioethicist James Hughes suggests that one possible ethical route to the genetic manipulation of humans at early developmental stages is the building of computer models of the human genome, the proteins it specifies and the tissue engineering he argues that it also codes for. With the exponential progress in bioinformatics, Hughes believes that a virtual model of genetic expression in the human body will not be far behind and that it will soon be possible to accelerate approval of genetic modifications by simulating their effects on virtual humans. Public health professor Gregory Stock points to artificial chromosomes as an alleged safer alternative to existing genetic engineering techniques.
Genetic engineering
Genetic engineering is an important tool for natural scientists, with the creation of transgenic organisms one of the most important tools for analysis of gene function. Genes and other genetic information from a wide range of organisms can be inserted into bacteria for storage and modification, creating genetically modified bacteria in the process. Bacteria are cheap, easy to grow, clonal, multiply quickly, relatively easy to transform and can be stored at -80 °C almost indefinitely. Once a gene is isolated it can be stored inside the bacteria providing an unlimited supply for research.
Organisms are genetically engineered to discover the functions of certain genes. This could be the effect on the phenotype of the organism, where the gene is expressed or what other genes it interacts with. These experiments generally involve loss of function, gain of function, tracking and expression.Organisms can have their cells transformed with a gene coding for a useful protein, such as an enzyme, so that they will overexpress the desired protein. Mass quantities of the protein can then be manufactured by growing the transformed organism in bioreactor equipment using industrial fermentation, and then purifying the protein. Some genes do not work well in bacteria, so yeast, insect cells or mammalians cells can also be used. These techniques are used to produce medicines such as insulin, human growth hormone, and vaccines, supplements such as tryptophan, aid in the production of food (chymosin in cheese making) and fuels. Other applications with genetically engineered bacteria could involve making them perform tasks outside their natural cycle, such as making biofuels, cleaning up oil spills, carbon and other toxic waste and detecting arsenic in drinking water. Certain genetically modified microbes can also be used in biomining and bioremediation, due to their ability to extract heavy metals from their environment and incorporate them into compounds that are more easily recoverable.
Wrongful birth
In the past, plaintiffs have had to prove cause by showing that if the defendant had not been negligent, the child would have been normal. Under this standard, the defendant may argue that even if she or he failed to diagnose an existing fetus with a genetic or developmental abnormality, she or he did not cause the parents or fetus to have mutated genes or the fetus to develop the abnormality. Once the fetus is determined to have an abnormality, the doctor may not be able to treat the fetus, making the abnormality inevitable. If the doctor fails to diagnose the plaintiff’s risk of transmitting a genetic disease, or fails to inform the plaintiff of that risk, then it is the combination of the parents’ genetic mutations and choice to have a child that most directly results in the conception of an abnormal child. Because of difficulties in proving cause under this standard some courts disallowed wrongful birth suits.
Human germline engineering
Human germline engineering is the process by which the genome of an individual is edited in such a way that the change is heritable. This is achieved through genetic alterations within the germinal cells, or the reproductive cells, such as the oocyte and spermatogonium. Human germline engineering should not be confused with gene therapy. Gene therapy consists of altering somatic cells, which are all cells in the body that are not involved in reproduction. While gene therapy does change the genome of the targeted cells, these cells are not within the germline, so the alterations are not heritable and cannot be passed on to the next generation.
Human germline engineering
There are many prospective uses such as curing genetic diseases and disorders. If perfected, somatic gene editing can promise helping people who are sick. In the first study published regarding human germline engineering, the researchers attempted to edit the "HBB" gene which codes for the human β-globin protein. Mutations in the "HBB" gene result in the disorder β-thalassaemia, which can be fatal. Perfect editing of the genome in patients who have these "HBB" mutations would result in copies of the gene which do not possess any mutations, effectively curing the disease. The importance of editing the germline would be to pass on this normal copy of the "HBB" genes to future generations.
Genetic programming
Meta-genetic programming is the proposed meta learning technique of evolving a genetic programming system using genetic programming itself. It suggests that chromosomes, crossover, and mutation were themselves evolved, therefore like their real life counterparts should be allowed to change on their own rather than being determined by a human programmer. Meta-GP was formally proposed by Jürgen Schmidhuber in 1987. Doug Lenat's Eurisko is an earlier effort that may be the same technique. It is a recursive but terminating algorithm, allowing it to avoid infinite recursion. In the "autoconstructive evolution" approach to meta-genetic programming, the methods for the production and variation of offspring are encoded within the evolving programs themselves, and programs are executed to produce new programs to be added to the population.
Genome editing
Genetic engineering as a method of introducing new genetic elements into organisms has been around since the 1970's. 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.
Genome editing
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.
Gene therapy
In germline gene therapy (GGT), germ cells (sperm or egg cells) are modified by the introduction of functional genes into their genomes. Modifying a germ cell causes all the organism's cells to contain the modified gene. The change is therefore heritable and passed on to later generations. Australia, Canada, Germany, Israel, Switzerland, and the Netherlands prohibit GGT for application in human beings, for technical and ethical reasons, including insufficient knowledge about possible risks to future generations and higher risks versus SCGT. The US has no federal controls specifically addressing human genetic modification (beyond FDA regulations for therapies in general).
CRISPR
Policy regulations for the CRISPR/cas9 system vary around the globe. In February 2016, British scientists were given permission by regulators to genetically modify human embryos by using CRISPR-Cas9 and related techniques. However, researchers were forbidden from implanting the embryos and the embryos were to be destroyed after seven days.
Autism rights movement
Since those in the autism rights movement see autism as a natural human variation and not a disorder, they are opposed to attempts to eliminate autism. In particular, there is opposition to prenatal genetic testing of autism in unborn fetuses, which some believe might be possible in the future (see Heritability of autism). Some worry that this can prevent autistic people from being born. On February 23, 2005 Joseph Buxbaum of the Autism Genome Project at the Icahn School of Medicine at Mount Sinai said there could be a prenatal test for autism within 10 years. However, the genetics of autism have proven to be extremely complex. In any case, the Autistic Genocide Clock was started in response to this, which counts down to 10 years after Buxbaum made this announcement. The public has started to debate the ethics involved in the possible elimination of a genotype that has liabilities and advantages, which may be seen as tampering with natural selection.
Mutants (Judge Dredd storyline)
As time went on, the Mutant Segregation Act (named in prog 603) was shown to cover people who had contracted a gene-altering virus, dwarfs, and people who had even the slightest genetic abnormality, if they were screened by someone in a bad mood. Psychics were exempt as they were forcibly drafted in Justice Department's Psi-Division. Under Mega-City law, any norm who harboured a mutant was himself guilty of a crime and liable to strict penalties. Since a normal woman could still give birth to a mutant child, the parents of mutated offspring would sometimes go to great lengths to conceal the birth (or, at least, its abnormality) and raise their child in secret. Detection of a mutant foetus in a routine pregnancy scan would result in mandatory abortion; detection of a mutant birth would result in the parents being forced to choose between exile to the Cursed Earth, the "euthanasia" of the child, or the mutant being deported to Cursed Earth farming camps.
Sperm-mediated gene transfer
The potential use of sperm-mediated gene transfer for embryo somatic gene therapy is a possibility for future research. Embryo somatic gene therapy would be advantageous because there seems to be an inverse correlation between the age of the patient and the effectiveness of gene therapy. Therefore, the possibility of gene therapy treatment before irreversible damage occurs would be ideal. A majority of the experiments that report successful SMGT provide evidence of post-fertilization transfer and maintenance of transgenes. SMGT has potential advantages of being a simple and cost-effective method of gene therapy, especially in contrast with pronuclear microinjection, another transgenic technique. Nevertheless, despite some successes and its potential utility, SMGT is not yet established as a reliable form of genetic modification.
Designer baby
Gene therapy is the use of DNA as a pharmaceutical agent to treat disease. Gene therapy was first conceptualized in 1972, with the authors urging caution before commencing gene therapy studies in humans. The first FDA-approved gene therapy experiment in the United States occurred in 1990, on a four-year-old girl named, Ashanti DeSilva, she was treated for ADA-SCID. This is a disease that had left her defenseless against infections spreading throughout her body. Dr. W French Anderson was a major lead on this clinical trial, he worked for the National Heart, Lung, and Blood Institute Since then, over 1,700 clinical trials have been conducted using a number of techniques for gene therapy.
Genetic engineering techniques
Traditional methods of genetic engineering generally insert the new genetic material randomly within the host genome. This can impair or alter other genes within the organism. Methods were developed that inserted the new genetic material into specific sites within an organism genome. Early methods that targeted genes at certain sites within a genome relied on homologous recombination. 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 knocked out. It has also been possible to knock in genes or alter gene expression patterns.
Human germline engineering
The first attempt to edit the human germline was reported in 2015, when a group of Chinese scientists used the gene editing technique CRISPR/Cas9 to edit single-celled, non-viable embryos to see the effectiveness of this technique. This attempt was rather unsuccessful; only a small fraction of the embryos successfully spliced the new genetic material and many of the embryos contained a large amount of random mutations. The non-viable embryos that were used contained an extra set of chromosomes, which may have been problematic. In 2016, another similar study was performed in China which also used non-viable embryos with extra sets of chromosomes. This study showed very similar results to the first; there were successful integrations of the desired gene, yet the majority of the attempts failed, or produced undesirable mutations.
Genetic diagnosis of intersex
Preimplantation genetic diagnosis (PGD or PIGD) refers to genetic evaluation of embryos and oocytes prior to implantation. When used to screen for a specific genetic condition, the method also makes it possible to select embryos with intersex conditions for termination. Some national authorities, such as the UK Human Fertilization and Embryology Authority, maintain lists of conditions for which PGD is permissible, including intersex conditions such as 5 alpha reductase deficiency, androgen insensitivity syndrome, congenital adrenal hyperplasia and others.
Mitochondrial disease
Spindle transfer, where the nuclear DNA is transferred to another healthy egg cell leaving the defective mitochondrial DNA behind, is a potential treatment procedure that has been successfully carried out on monkeys. Using a similar pronuclear transfer technique, researchers at Newcastle University led by Douglass Turnbull successfully transplanted healthy DNA in human eggs from women with mitochondrial disease into the eggs of women donors who were unaffected. In such cases, ethical questions have been raised regarding biological motherhood, since the child receives genes and gene regulatory molecules from two different women. Using genetic engineering in attempts to produce babies free of mitochondrial disease is controversial in some circles and raises important ethical issues. A male baby was born in Mexico in 2016 from a mother with Leigh syndrome using spindle transfer.
History of eugenics
In 2006, Richard Dawkins stated that breeding humans for traits is possible and society should not be afraid to debate the ethical differences between breeding a child for an ability versus forcing a child to gain an ability through training. Nathaniel C. Comfort, Professor at the Institute of the History of Medicine at the Johns Hopkins University, published in his 2012 book, "The Science of Human Perfection: How Genes Became the Heart of American Medicine", "The eugenic impulse drives us to eliminate disease, live longer and healthier, with greater intelligence, and a better adjustment to the conditions of society." Comfort claims that the question is not whether this eugenic impulse should exist or even whether the modern genetic movement should be called eugenics because these things "just are". Additionally, Dr Nathaniel Comfort claims, "the health benefits, the intellectual thrill and the profits of genetic biomedicine are too great for us to do otherwise." Bio-ethicist Stephen Wilkinson of Keele University and Honorary Research Fellow Eve Garrard at the University of Manchester, claim that some aspects of modern genetics can be classified as eugenics, but this classification does not inherently make modern genetics immoral. In a co-authored publication by Keele University, they stated that "[e]ugenics doesn't seem always to be immoral, and so the fact that PGD, and other forms of selective reproduction, might sometimes technically be eugenic, isn't sufficient to show that they’re wrong."
Lulu and Nana controversy
The Lulu and Nana controversy revolves around twin Chinese girls born in November 2018, who have been given the pseudonyms Lulu () and Nana (). According to the researcher, He Jiankui (Western name order: Jiankui He), the twins are the world's first germline genetically edited babies. He Jiankui has reported that the girls were born healthy. The girls' parents were participants in a clinical project run by He, in which he offered standard in vitro fertilization services and in addition, used CRISPR-Cas9, a technology that can modify DNA, to modify the "CCR5" gene in the embryos that were generated, to attempt to confer genetic resistance to the HIV virus. The clinical project was conducted secretly until November 2018.
Assisted reproductive technology
Germline modification is considered a more ethically and morally acceptable treatment when one or both of the parents is a carrier for a harmful trait and is treated to improve the genotype and safety of the future generations. When the treatment is used for this purpose, it can fill the gaps that other technologies may not be able to accomplish. The American National Academy of Sciences and National Academy of Medicine gave qualified support to human genome editing in 2017 once answers have been found to safety and efficiency problems "but only for serious conditions under stringent oversight." Germline modification would be more practical if sampling methods were less destructive and used the polar bodies rather than embryos. In 2018, the Nuffield Council on Bioethics issued a report which concluded that under certain circumstances, editing of the DNA of human embryos could be acceptable. The Nuffield Council is a British independent organisation that evaluates ethical questions in medicine and biology.
Off-target genome editing
Off-target genome editing refers to nonspecific and unintended genetic modifications that can arise through the use of engineered nuclease technologies such as: clustered, regularly interspaced, short palindromic repeats (CRISPR)-Cas9, transcription activator-like effector nucleases (TALEN), meganucleases, and zinc finger nucleases (ZFN). These tools use different mechanisms to bind a predetermined sequence of DNA (“target”), which they cleave (or "cut"), creating a double-stranded chromosomal break (DSB) that summons the cells DNA repair mechanisms (non-homologous end joining (NHEJ) and homologous recombination (HR)) and leads to site-specific modifications. If these complexes do not bind at the target, often a result of homologous sequences and/or mismatch tolerance, they will cleave off-target DSB and cause non-specific genetic modifications. Specifically, off-target effects consist of unintended point mutations, deletions, insertions inversions, and translocations.
Lulu and Nana controversy
He, the researcher, took sperm and eggs from the couples, performed in vitro fertilization with them, and then edited the genomes of the embryos using CRISPR/Cas9. The editing targeted a gene, "CCR5", that codes for a protein that HIV uses to enter cells. He was trying to create a specific mutation in the gene, (CCR5 Δ32), that few people naturally have — that possibly confers innate resistance to HIV, as seen in the case of the Berlin Patient. He said that the girls still carried functional copies of CCR5 along with disabled CCR5 given mosaicism inherent in the present state of the art in germ-line editing. There are forms of HIV that use a different receptor instead of CCR5, and the work that He did could not protect Lulu and Nana from those forms of HIV.
Genetically modified organism
Systems have been developed to create transgenic organisms in a wide variety of other animals. Chickens have been genetically modified for a variety of purposes. This includes studying embryo development, preventing the transmission of bird flu and providing evolutionary insights using reverse engineering to recreate dinosaur-like phenotypes. A GM chicken that produces the drug Kanuma, an enzyme that treats a rare condition, in its egg passed regulatory approval in 2015. Genetically modified frogs, in particular "Xenopus laevis" and "Xenopus tropicalis", are used in development biology. GM frogs can also being used as pollution sensors, especially for endocrine disrupting chemicals. There are proposals to use genetic engineering to control cane toads in Australia.
Genetically modified organism
A genetically modified organism (GMO) is any organism whose genetic material has been altered using genetic engineering techniques. The exact definition of a genetically modified organism and what constitutes genetic engineering varies, with the most common being an organism altered in a way that "does not occur naturally by mating and/or natural recombination". A wide variety of organisms have been genetically modified (GM), from animals to plants and microorganisms. Genes have been transferred within the same species, across species (creating transgenic organisms) and even across kingdoms. New genes can be introduced, or endogenous genes can be enhanced, altered or knocked out.
Genetic engineering
Germline gene therapy would result in any change being inheritable, which has raised concerns within the scientific community. In 2015, CRISPR was used to edit the DNA of non-viable human embryos, leading scientists of major world academies to call for a moratorium on inheritable human genome edits. There are also concerns that the technology could be used not just for treatment, but for enhancement, modification or alteration of a human beings' appearance, adaptability, intelligence, character or behavior. The distinction between cure and enhancement can also be difficult to establish. In November 2018, He Jiankui announced that he had edited the genomes of two human embryos, to attempt to disable the "CCR5" gene, 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.
Genetic disorder
The basic aspects of a genetic disorder rests on the inheritance of genetic material. With an in depth family history, it is possible to anticipate possible disorders in children which direct medical professionals to specific tests depending on the disorder and allow parents the chance to prepare for potential lifestyle changes, anticipate the possibility of stillbirth, or contemplate termination. Prenatal diagnosis can detect the presence of characteristic abnormalities in fetal development through ultrasound, or detect the presence of characteristic substances via invasive procedures which involve inserting probes or needles into the uterus such as in amniocentesis.
Genome editing
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.
Designer baby
Germline modification has been around since the 1980s, as there have been successful animal trials dating back to that time. In order for germline modification to be successful, medical professionals must know how to introduce a gene into the patient's’ cell and the germline so that it will be transferred subsequent generations and still maintain the proper functionality. The way in which genes are integrated into the DNA is what determines that difference between germline modification and somatic cell modification. In order to be transferred to subsequent generations, these changes need to be carried out through the development of germ cells. Changes in the germline result in permanent and heritable changes to the DNA. While amplification of positive effects would occur, there is also the risk that amplification of possible negative effects would also occur. Since the results are generational, it is more complicated to study the long-term effects and therefore it is not a simple task to figure out if the benefits of germline modification outweigh the harm. Allowing families to have the ability to design their children and select for desirable traits is another major concern that germline modification presents.
Gene therapy
Possible regulatory schemes include a complete ban, provision to everyone, or professional self-regulation. The American Medical Association’s Council on Ethical and Judicial Affairs stated that "genetic interventions to enhance traits should be considered permissible only in severely restricted situations: (1) clear and meaningful benefits to the fetus or child; (2) no trade-off with other characteristics or traits; and (3) equal access to the genetic technology, irrespective of income or other socioeconomic characteristics."
Genetically modified mouse
There are two basic technical approaches to produce genetically modified mice. The first involves pronuclear injection into a single cell of the mouse embryo, where it will randomly integrate into the mouse genome. This method creates a transgenic mouse and is used to insert new genetic information into the mouse genome or to over-express endogenous genes. The second approach, pioneered by Oliver Smithies and Mario Capecchi, involves modifying embryonic stem cells with a DNA construct containing DNA sequences homologous to the target gene. Embryonic stem cells that recombine with the genomic DNA are selected for and they are then injected into the mice blastocysts. This method is used to manipulate a single gene, in most cases "knocking out" the target gene, although more subtle genetic manipulation can occur (e.g. only changing single nucleotides).
Genetically modified animal
A number of techniques are available for inserting the isolated gene into the host genome. With animals DNA is generally inserted into using microinjection, where it can be injected through the cell's nuclear envelope directly into the nucleus, or through the use of viral vectors. The first transgenic animals were produced by injecting viral DNA into embryos and then implanting the embryos in females. It is necessary to ensure that the inserted DNA is present in the embryonic stem cells. The embryo would develop and it would be hoped that some of the genetic material would be incorporated into the reproductive cells. Then researchers would have to wait until the animal reached breeding age and then offspring would be screened for presence of the gene in every cell, using PCR, Southern hybridization, and DNA sequencing.
Birth defect
Genetic causes of birth defects include inheritance of abnormal genes from the mother or the father, as well as new mutations in one of the germ cells that gave rise to the fetus. Male germ cells mutate at a much faster rate than female germ cells, and as the father ages, the DNA of the germ cells mutates quickly. If an egg is fertilized with sperm that has damaged DNA, there is a possibility that the fetus could develop abnormally.
Essential gene
Gene knockout experiments are not possible or at least not ethical in humans. However, natural mutations have led to the identification of mutations that lead to early embryonic or later death. Note that many genes in humans are not absolutely essential for survival but can cause severe disease when mutated. Such mutations are catalogued in the Online Mendelian Inheritance in Man (OMIM) database. In a computational analysis of genetic variation and mutations in 2,472 human orthologs of known essential genes in the mouse, Georgi et al. found strong, purifying selection and comparatively reduced levels of sequence variation, indicating that these human genes are essential too.
Whole genome sequencing
Currently available newborn screening for childhood diseases allows detection of rare disorders that can be prevented or better treated by early detection and intervention. Specific genetic tests are also available to determine an etiology when a child's symptoms appear to have a genetic basis. Full genome sequencing, in addition has the potential to reveal a large amount of information (such as carrier status for autosomal recessive disorders, genetic risk factors for complex adult-onset diseases, and other predictive medical and non-medical information) that is currently not completely understood, may not be clinically useful to the child during childhood, and may not necessarily be wanted by the individual upon reaching adulthood.
Genetically modified food controversies
The first genetically modified crops were made with transgenic approaches, introducing foreign genes and sometimes using bacteria to transfer the genes. In the US, these foreign genetic elements placed the resulting plant under the jurisdiction of the USDA under the Plant Protection Act. However, as of 2010, newer genetic engineering technologies like genome editing have allowed scientists to modify plant genomes without adding foreign genes, thus escaping USDA regulation. Critics have called for regulation to be changed to keep up with changing technology.
Gene therapy
Gene editing is a potential approach to alter the human genome to treat genetic diseases, viral diseases, and cancer. these approaches were still years from being medicine.
Gene drive
In December 2015, scientists of major world academies called for a moratorium on inheritable human genome edits that would affect the germline, including those related to CRISPR-Cas9 technologies, but supported continued basic research and gene editing that would not affect future generations. In February 2016, British scientists were given permission by regulators to genetically modify human embryos by using CRISPR-Cas9 and related techniques on condition that the embryos were destroyed in seven days. In June 2016, the US National Academies of Sciences, Engineering, and Medicine released a report on their "Recommendations for Responsible Conduct" of gene drives.
Genetically modified organism
A mushroom has been gene edited to resist browning, giving it a longer shelf life. The process used CRISPR to knock out a gene that encodes polyphenol oxidase. As it didn't introduce any foreign DNA into the organism it was not deemed to be regulated under existing GMO frameworks and as such is the first CRISPR-edited organism to be approved for release. This has intensified debates as to whether gene-edited organisms should be considered genetically modified organisms and how they should be regulated.
Genetically modified organism
Humans have domesticated plants and animals since around 12,000 BCE, using selective breeding or artificial selection (as contrasted with natural selection). The process of selective breeding, in which organisms with desired traits (and thus with the desired genes) are used to breed the next generation and organisms lacking the trait are not bred, is a precursor to the modern concept of genetic modification. Various advancements in genetics allowed humans to directly alter the DNA and therefore genes of organisms. In 1972 Paul Berg created the first recombinant DNA molecule when he combined DNA from a monkey virus with that of the lambda virus.
Designer baby
Genetics explains the process of parents passing down certain genes to their children. Genes are inherited from both biological parents, and each gene expresses a specific trait. The traits expressed by genes can be something physically seen—such as hair color, eye color, or height—or can be things such as diseases and disorders.
Designer baby
Basic processing can be achieved through replacement of a mutated gene, inactivation of a mutated gene, or introduction of a new gene to help fight a disease caused by mutation. Secondly, gene doping is a procedure of gene therapy that modulates gene expression of a particular gene. This procedure is mainly used to improve athletic ability for sporting events. This is a genetic form of human enhancement that is able to treat muscle-wasting disorders. It is a highly controversial procedure because the results do nothing unusual to the bloodstream, so athletic officials would be unable to detect chemicals in a blood or urine test. An example of gene doping would be proving athlete with erythropoietin (EPO), a hormone that increases the red blood cell count. Lastly, viral vectors are able to mimic the methods of a normal virus in the human body to introduce favorable genes into a human cell. For instance, scientists are able to positively change the host's genome by removing the genes that cause disease from a virus and replacing it with genes of the desired trait (“Types of Gene Therapy”).
Genome editing
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.
Epigenome editing
Epigenome editing or Epigenome engineering is a type of genetic engineering in which the epigenome is modified at specific sites using engineered molecules targeted to those sites (as opposed to whole-genome modifications). Whereas gene editing involves changing the actual DNA sequence itself, epigenetic editing involves modifying and presenting DNA sequences to proteins and other DNA binding factors that influence DNA function. By "editing” epigenomic features in this manner, researchers can determine the exact biological role of an epigenetic modification at the site in question.
Behavioural genetics
The Human Genome Project has allowed scientists to directly genotype the sequence of human DNA nucleotides. Once genotyped, genetic variants can be tested for association with a behavioural phenotype, such as mental disorder, cognitive ability, personality, and so on.Some behavioural genetic designs are useful not to understand genetic influences on behaviour, but to control for genetic influences to test environmentally-mediated influences on behaviour. Such behavioural genetic designs may be considered a subset of natural experiments, quasi-experiments that attempt to take advantage of naturally occurring situations that mimic true experiments by providing some control over an independent variable. Natural experiments can be particularly useful when experiments are infeasible, due to practical or ethical limitations.
Genetic policy in the United States
Genetic testing is the analysis of human genes, proteins, and certain metabolites, in order to detect inherited disease-related propensities. These tests can predict the risk of disease in adults, as well as establish prenatal and infant prognoses. The benefits can be substantial, but so can the risks. The possible adverse consequences of genetic tests include discrimination in employment and health insurance, and breaches of privacy. Government policies are therefore needed to assure the proper use of genetic tests. The first piece of federal legislation came into effect in 2000.
Human germline engineering
The creation of genetically modified humans may have been performed in the mid-1990s, in which a 1997 study published in The Lancet claimed, “the first case of human germ-line genetic modification resulting in normal healthy children.”. In November 2018, researcher Jiankui He claimed that he had created the first human genetically edited babies, known by their pseudonyms, Lulu () and Nana ().
Botany
Epigenetics is the study of heritable changes in gene function that cannot be explained by changes in the underlying DNA sequence but cause the organism's genes to behave (or "express themselves") differently. One example of epigenetic change is the marking of the genes by DNA methylation which determines whether they will be expressed or not. Gene expression can also be controlled by repressor proteins that attach to silencer regions of the DNA and prevent that region of the DNA code from being expressed. Epigenetic marks may be added or removed from the DNA during programmed stages of development of the plant, and are responsible, for example, for the differences between anthers, petals and normal leaves, despite the fact that they all have the same underlying genetic code. Epigenetic changes may be temporary or may remain through successive cell divisions for the remainder of the cell's life. Some epigenetic changes have been shown to be heritable, while others are reset in the germ cells.
Woolly mammoth
In April 2015, Swedish scientists published the complete genome (nuclear DNA sequence) of the woolly mammoth. Several projects are working on gradually replacing the genes in elephant cells with mammoth genes. One such project is that of Harvard University geneticist George M. Church —who is funded by the Long Now Foundation, which is attempting to create a mammoth-elephant hybrid using DNA from frozen mammoth carcasses. According to the researchers, a mammoth cannot be recreated, but they will try to eventually grow a hybrid elephant with some woolly mammoth traits in an "artificial womb". The Harvard University team is attempting to study the animals' characteristics "in vitro" by replacing or editing some specific mammoth genes into Asian elephant skin cells called fibroblasts that have the potential to become embryonic stem cells. By March 2015 and using the new CRISPR DNA editing technique, Church's team had some woolly mammoth genes edited into the genome of an Asian elephant; Focusing on cold-resistance initially, the target genes are for the external ear size, subcutaneous fat, hemoglobin, and hair attributes. By February 2017, Church's team had made 45 substitutions to the elephant genome. So far his work focuses solely on single cells.
Genetic engineering techniques
Genome editing uses artificially engineered nucleases that create specific double-stranded breaks at desired locations in the genome. The breaks are subject to cellular DNA repair processes that can be exploited for targeted gene knock-out, correction or insertion at high frequencies. If a donor DNA containing the appropriate sequence (homologies) is present, then new genetic material containing the transgene will be integrated at the targeted site with high efficiency by homologous recombination. There are four families of engineered nucleases: meganucleases, ZFNs, transcription activator-like effector nucleases (TALEN), the CRISPR/Cas (clustered regularly interspaced short palindromic repeat/CRISPRassociated protein (e.g. CRISPR/Cas9). Among the four types, TALEN and CRISPR/Cas are the two most commonly used. Recent advances have looked at combining multiple systems to exploit the best features of both (e.g. megaTAL that are a fusion of a TALE DNA binding domain and a meganuclease). Recent research has also focused on developing strategies to create gene knock-out or corrections without creating double stranded breaks (base editors).
Human germline engineering
As it stands, there is much controversy surrounding human germline engineering. Editing the genes of human embryos is very different, and raises great social and ethical concerns. The scientific community, and global community, are quite divided regarding whether or not human germline engineering should be practiced or not. It is currently banned in many of the leading, developed countries, and highly regulated in the others due to ethical issues. The large debate lies in the possibility of eugenics if human germline engineering were to be practiced clinically. This topic is hotly debated because the side opposing human germline modification believes that it will be used to create humans with "perfect", or "desirable" traits. Those in favor of human germline modification see it as a potential medical tool, or a medical cure for certain diseases that lie within the genetic code. There is a debate as to if this is morally acceptable as well. Such debate ranges from the ethical obligation to use safe and efficient technology to prevent disease to seeing actual benefit in genetic disabilities. While typically there is a clash between religion and science, the topic of human germline engineering has shown some unity between the two fields. Several religious positions have been published with regards to human germline engineering. According to them, many see germline modification as being more moral than the alternative, which would be either discarding of the embryo, or birth of a diseased human. The main conditions when it comes to whether or not it is morally and ethically acceptable lie within the intent of the modification, and the conditions in which the engineering is done.
Genome editing
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. 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. In addition, gene functions can be studied using stem cells with engineered nucleases.
Biotechnology
Genetically modified foods are foods produced from organisms that have had specific changes introduced into their DNA with the methods of genetic engineering. These techniques have allowed for the introduction of new crop traits as well as a far greater control over a food's genetic structure than previously afforded by methods such as selective breeding and mutation breeding. Commercial sale of genetically modified foods began in 1994, when Calgene first marketed its Flavr Savr delayed ripening tomato. To date most genetic modification of foods have primarily focused on cash crops in high demand by farmers such as soybean, corn, canola, and cotton seed oil. These have been engineered for resistance to pathogens and herbicides and better nutrient profiles. GM livestock have also been experimentally developed; in November 2013 none were available on the market, but in 2015 the FDA approved the first GM salmon for commercial production and consumption.
Genome editing
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.
Genetic engineering
Humans have altered the genomes of species for thousands of years through selective breeding, or artificial selection as contrasted with natural selection. More recently, mutation breeding has used exposure to chemicals or radiation to produce a high frequency of random mutations, for selective breeding purposes. Genetic engineering as the direct manipulation of DNA by humans outside breeding and mutations has only existed since the 1970s. The term "genetic engineering" was first coined by Jack Williamson in his science fiction novel "Dragon's Island", published in 1951 – one year before DNA's role in heredity was confirmed by Alfred Hershey and Martha Chase, and two years before James Watson and Francis Crick showed that the DNA molecule has a double-helix structure – though the general concept of direct genetic manipulation was explored in rudimentary form in Stanley G. Weinbaum's 1936 science fiction story "Proteus Island".
Genetically modified organism
What constitutes a genetically modified organism (GMO) is not always clear and can vary widely. At its broadest it can include anything that has had its genes altered, including by nature. Taking a less broad view it can encompass every organism that has had its genes altered by humans, which would include all crops and livestock. In 1993 the "Encyclopedia Britannica" defined genetic engineering as "any of a wide range of techniques ... among them artificial insemination, "in vitro" fertilization ("e.g.", "test-tube" babies), sperm banks, cloning, and gene manipulation." The European Union (EU) included a similarly broad definition in early reviews, specifically mentioning GMOs being produced by "selective breeding and other means of artificial selection." They later excluded traditional breeding, in vitro fertilisation, induction of polyploidy, mutagenesis and cell fusion techniques that do not use recombinant nucleic acids or a genetically modified organism in the process.
Genetically modified crops
Genetically engineered crops have genes added or removed using genetic engineering techniques, originally including gene guns, electroporation, microinjection and agrobacterium. More recently, CRISPR and TALEN offered much more precise and convenient editing techniques.
Assisted reproductive technology
In November 2018, Jiankui He announced that he had edited the genomes of 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. Carl Zimmer compared the reaction to He's human gene editing experiment to the initial reactions and subsequent debate over mitochondrial replacement therapy (MRT) and the eventual regulatory approval of MRT in the United Kingdom.
Mark S. Gold
In an interview for the Congressional Quarterly (CQ Researcher), Gold stated that there is universal agreement that genes can be changed by exposure to drugs. He used the example of a person whose mother smoked when she was pregnant. This person had genetic receptors that were changed because of the exposure, making that person more likely to become addicted to nicotine. Intrauterine and early childhood exposure may also change risk trajectories for other drugs and food and become an acquired risk for obesity.
Gene
Genetic engineering is the modification of an organism's genome through biotechnology. Since the 1970s, a variety of techniques have been developed to specifically add, remove and edit genes in an organism. Recently developed genome engineering techniques use engineered nuclease enzymes to create targeted DNA repair in a chromosome to either disrupt or edit a gene when the break is repaired. The related term synthetic biology is sometimes used to refer to extensive genetic engineering of an organism.
Genetically modified sperm
In genetic modification, genes are inserted into living cells in order to change how proteins are created. A viral vector is often used to deliver the gene of interest to the chromosomes in the cell nucleus. Every daughter cell will reflect the genetic modification.
Genetic editing
Whereas traditional scholarly editing can be seen as constructing a new document drawing together and comparing many source documents to cast light on a work, genetic editing closely examines a single extant manuscript and traces back each aspect to cast light on the work.
Genetically modified animal
New technologies are making genetic modifications easier and more precise. Gene targeting techniques, which creates double-stranded breaks and takes advantage on the cells natural homologous recombination repair systems, have been developed to target insertion to exact locations. Genome editing uses artificially engineered nucleases that create breaks at specific points. There are four families of engineered nucleases: meganucleases, zinc finger nucleases, transcription activator-like effector nucleases (TALENs), and the Cas9-guideRNA system (adapted from CRISPR). TALEN and CRISPR are the two most commonly used and each has its own advantages. TALENs have greater target specificity, while CRISPR is easier to design and more efficient. The development of the CRISPR-Cas9 gene editing system has effectively halved the amount of time needed to develop genetically modified animals.
Transhuman Space
Human genetic engineering has advanced to the point that anyone—single individuals, same-sex couples, groups of three or more—can reproduce. The embryos can be allowed to be developed naturally, or they can undergo three levels of tinkering: 
1. "Genefixing", which corrects defects; 
2. "Upgrades", which boost natural abilities (Ishtar Upgrades are slightly more attractive than usual, Metanoia Upgrades are more intelligent, etc.); and... 
3. Full transition to "parahuman" status (Nyx Parahumans only need a few hours of sleep per week, Aquamorphs can live underwater, etc.) Another type of human genetic engineering, far more controversial, is the creation of bioroids, fully sentient slave races.
Genetically modified fish
Generally, genetic modification entails manipulation of DNA. The process is known as cisgenesis when a gene is transferred between organisms that could be conventionally bred, or transgenesis when a gene from one species is added to a different species. Gene transfer into the genome of the desired organism, as for fish in this case, requires a vector like a lentivirus or mechanical/physical insertion of the altered genes into the nucleus of the host by means of a micro syringe or a gene gun.
Biology and consumer behaviour
Epigenetics is referred to as the ‘new genetics’ and phenomenon of importance to marketers because it studies how our environment can influence our genes, and hence our behaviour. The theory of meiosis is that exact replicas of parents' genes are passed to their offspring, with no variation influence from the environment. However genes have a protein wrapping the gene that can influence the gene expression and therefore phenotypes to the environment. How we act and consume now affects our epigenome, and consequently our offspring’s genome. This supports Lamark’s theory, prior to Darwin, who initially proposed the theory of our genes changing with behaviour and experience. A study from the University of Auckland warned pregnant women against dieting due to the increased likelihood in their child acquiring eating disorders such as obesity, hence the way we consume food.
He Jiankui
He said that he used a preimplantation genetic diagnosis process on the embryos that were edited, where three to five single cells were removed and the editing was checked. He said that parents were offered the choice of using edited or unedited embryos.
Genome editing
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.
Genetically modified sperm
Genetic modification in humans is a contested issue due to the variety of social and ethical issues it raises. One such controversy is the ability to modify the genes of future offspring to decrease the likelihood for certain diseases or modify the expression of chosen traits. In a recent case, an American teenager successfully sued a sperm bank, because she had been born with fragile X syndrome. Some also cite the promotion of eugenics through certain applications of genetic modification, justifying the moratorium on research and funding in human trials in many countries.
Designer baby
A designer baby is a human embryo which has been genetically modified, usually following guidelines set by the parent or scientist, to produce desirable traits. This is done using various methods, such as germline engineering or preimplantation genetic diagnosis (PGD). This technology is the subject of ethical debate, bringing up the concept of genetically modified "superhumans" to interbreed with and eventually replace modern humans.
Genetic engineering
Genetic engineering is a process that alters the genetic structure of an organism by either removing or introducing DNA. Unlike traditional animal and plant breeding, which involves doing multiple crosses and then selecting for the organism with the desired phenotype, genetic engineering takes the gene directly from one organism and inserts it in the other. This is much faster, can be used to insert any genes from any organism (even ones from different domains) and prevents other undesirable genes from also being added.
Genome editing
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. In November 2018, Jiankui He 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.
Eugenics in the United States
One negative of genetic engineering is the practice of eliminating "undesirable traits" within humans and its ethics. This ultimately causes a link between genetic engineering and eugenics. This practice creates many social issues in society. Many people believe using genetic engineering to essentially "perfect" the human race is a damaging practice. For example, with current genetic tests, parents are able to test a fetus for any life-threatening diseases that may impact the child's life and then choose to abort the baby. The public fears this will cause issues due to the fact that practices like these may be used to eliminate entire groups of people, like the way Hitler used the idea. The basis of Hitler's movement was to create a superior Aryan race, he wanted to eliminate every other race. While he did not have the genetic engineering technology then, this technology could be used with similar tactics as Hitler with permanent modifications to human germ lines and the ability to terminate a pregnancy that won't produce the best baby. Genetic engineering can also lead to trait selection and enhancement in embryos. One dilemma with this application is that most genes have an effect on more than one area of the body. For example, there is a gene that deals with memory, when scientists altered this gene to improve memory and learning in mice, it also increased their sensitivity to pain. There is also the issue of whether it is ethical to do such a thing to embryos because they cannot consent to the procedure. This also leads to issues within a socio-economic standpoint. Many people see this as an opportunity for the rich to continue to improve their children when the poor are left to "suffer" with their "undesirable" genes.
Genetic engineering
The new genetic material can be inserted randomly within the host genome or targeted to a specific location. The technique of gene targeting uses homologous recombination to make desired changes to a specific endogenous gene. This tends to occur at a relatively low frequency in plants and animals and generally requires the use of selectable markers. The frequency of gene targeting can be greatly enhanced through genome editing. Genome editing uses artificially engineered nucleases that create specific double-stranded breaks at desired locations in the genome, and use the cell’s endogenous mechanisms to repair the induced break by the natural processes of homologous recombination and nonhomologous end-joining. There are four families of engineered nucleases: meganucleases, zinc finger nucleases, transcription activator-like effector nucleases (TALENs), and the Cas9-guideRNA system (adapted from CRISPR). TALEN and CRISPR are the two most commonly used and each has its own advantages. TALENs have greater target specificity, while CRISPR is easier to design and more efficient. In addition to enhancing gene targeting, engineered nucleases can be used to introduce mutations at endogenous genes that generate a gene knockout.
Pseudogene
Various mutations (such as indels and nonsense mutations) can prevent a gene from being normally transcribed or translated, and thus the gene may become less- or non-functional or "deactivated". These are the same mechanisms by which non-processed genes become pseudogenes, but the difference in this case is that the gene was not duplicated before pseudogenization. Normally, such a pseudogene would be unlikely to become fixed in a population, but various population effects, such as genetic drift, a population bottleneck, or, in some cases, natural selection, can lead to fixation. The classic example of a unitary pseudogene is the gene that presumably coded the enzyme L-gulono-γ-lactone oxidase (GULO) in primates. In all mammals studied besides primates (except guinea pigs), GULO aids in the biosynthesis of ascorbic acid (vitamin C), but it exists as a disabled gene (GULOP) in humans and other primates. Another more recent example of a disabled gene links the deactivation of the caspase 12 gene (through a nonsense mutation) to positive selection in humans.
Cas9
While genomic editing in eukaryotic cells has been possible using various methods since the 1980s the methods employed had proved to be inefficient and impractical to implement on a larger scale. Genomic editing leads to irreversible changes to the gene. Working like genetic scissors, the Cas9 nuclease opens both strands of the targeted sequence of DNA to introduce the modification by one of two methods. Knock-in mutations, facilitated via Homology Directed Repair, is the traditional pathway of targeted genomic editing approaches. This allows for the introduction of targeted DNA damage and repair. HDR employs the use of similar DNA sequences to drive the repair of the break via the incorporation of exogenous DNA to function as the repair template. This method relies on the periodic and isolated occurrence of DNA damage at the target site in order for a repair to commence. Knock-out mutations caused by Cas9/CRISPR results in the repair of the double-strand break by means of NHEJ (Non-Homologous End Joining). NHEJ can often result random deletions or insertions at the repair site disrupting or altering gene functionality. Therefore, genomic engineering by CRISPR/Cas9 gives researches the ability to generated targeted random gene disruption. Because of this, the precision of genomic editing is a great concern. With the discovery of CRISPR and specifically the Cas9 nuclease molecule, efficient and highly selective editing is now a reality. Cas9 allows for a reliable method of creating a targeted break at a specific location as designated by the crRNA and tracrRna guide strands. Cas9 derived from "S. pyogenes" has facilitated the targeted genomic modification in eukaryotic cells. The ease by which researches can insert Cas9 and template RNA in order to silence or cause point mutations on specific loci has proved invaluable to the quick and efficient mapping of genomic models and biological processes associated with various genes in a variety of eukaryotes. New engineered variant of the Cas9 nuclease have been developed that significantly reduce off-target manipulation. Called spCas9-HF1 (Streptococcus pyogenes Cas9 High Fidelity 1), has a success rate of modification in vivo of 85% and undetectable off-target manipulations as measured by genome wide break capture and targeted sequencing methods used to measure total genomic changes.
Designer baby
There are risks associated with genetic modifications to any organism. When focusing on the ethics behind this treatment, medical professionals and clinical ethicists take many factors into consideration. They look at whether or not the goal and outcome of the treatment are supposed to impact an individual and their family lineage or a group of people. The main ethical issue with pure germline modification is that these types of treatments will produce a change that can be passed down to future generations and therefore any error, known or unknown, will also be passed down and will affect the offspring. New diseases may be introduced accidentally.