designer baby designer baby a designer baby is a baby whose genetic makeup has been selected or altered, often to exclude a particular gene or to remove genes associated with disease. this process usually involves analysing a wide range of human embryos to identify genes associated with particular diseases and characteristics, and selecting embryos that have the desired genetic makeup; a process known as preimplantation genetic diagnosis. screening for single genes is commonly practiced, and polygenic screening is offered by a few companies. other methods by which a baby's genetic information can be altered involve directly editing the genome before birth, which is not routinely performed and only one instance of this is known to have occurred as of 2019, where chinese twins lulu and nana were edited as embryos, causing widespread criticism. part of a series ongenetic engineering genetically modified organisms bacteria viruses animals mammals fish insects plants maize/corn rice soybean potato history and regulation history regulation substantial equivalence cartagena protocol on biosafety process techniques molecular cloning recombinant dna gene delivery transformation transfection transduction genome editing talen crispr applications genetically modified crops food gene therapy designer baby controversies genetically modified food controversies gmo conspiracy theories pusztai affair séralini affair starlink corn recall he jiankui affair genetically altered embryos can be achieved by introducing the desired genetic material into the embryo itself, or into the sperm and/or egg cells of the parents; either by delivering the desired genes directly into the cell or using gene-editing technology. this process is known as germline engineering and performing this on embryos that will be brought to term is typically prohibited by law. editing embryos in this manner means that the genetic changes can be carried down to future generations, and since the technology concerns editing the genes of an unborn baby, it is considered controversial and is subject to ethical debate. while some scientists condone the use of this technology to treat disease, concerns have been raised that this could be translated into using the technology for cosmetic purposes and enhancement of human traits. pre-implantation genetic diagnosis main article: pre-implantation genetic diagnosis pre-implantation genetic diagnosis (pgd or pigd) is a procedure in which embryos are screened prior to implantation. the technique is used alongside in vitro fertilisation (ivf) to obtain embryos for evaluation of the genome – alternatively, ovocytes can be screened prior to fertilisation. the technique was first used in 1989. pgd is used primarily to select embryos for implantation in the case of possible genetic defects, allowing identification of mutated or disease-related alleles and selection against them. it is especially useful in embryos from parents where one or both carry a heritable disease. pgd can also be used to select for embryos of a certain sex, most commonly when a disease is more strongly associated with one sex than the other (as is the case for x-linked disorders which are more common in males, such as haemophilia). infants born with traits selected following pgd are sometimes considered to be designer babies. one application of pgd is the selection of 'saviour siblings', children who are born to provide a transplant (of an organ or group of cells) to a sibling with a usually life-threatening disease. saviour siblings are conceived through ivf and then screened using pgd to analyze genetic similarity to the child needing a transplant, to reduce the risk of rejection. process process of pre-implantation genetic diagnosis. in vitro fertilisation involves either incubation of sperm and oocyte together, or injection of sperm directly into the oocyte. pcr - polymerase chain reaction, fish - fluorescent in situ hybridisation. embryos for pgd are obtained from ivf procedures in which the oocyte is artificially fertilised by sperm. oocytes from the woman are harvested following controlled ovarian hyperstimulation (coh), which involves fertility treatments to induce production of multiple oocytes. after harvesting the oocytes, they are fertilised in vitro, either during incubation with multiple sperm cells in culture, or via intracytoplasmic sperm injection (icsi), where sperm is directly injected into the oocyte. the resulting embryos are usually cultured for 3–6 days, allowing them to reach the blastomere or blastocyst stage. once embryos reach the desired stage of development, cells are biopsied and genetically screened. the screening procedure varies based on the nature of the disorder being investigated. polymerase chain reaction (pcr) is a process in which dna sequences are amplified to produce many more copies of the same segment, allowing screening of large samples and identification of specific genes. the process is often used when screening for monogenic disorders, such as cystic fibrosis. another screening technique, fluorescent in situ hybridisation (fish) uses fluorescent probes which specifically bind to highly complementary sequences on chromosomes, which can then be identified using fluorescence microscopy. fish is often used when screening for chromosomal abnormalities such as aneuploidy, making it a useful tool when screening for disorders such as down syndrome. following the screening, embryos with the desired trait (or lacking an undesired trait such as a mutation) are transferred into the mother's uterus, then allowed to develop naturally. regulation pgd regulation is determined by individual countries' governments, with some prohibiting its use entirely, including in austria, china, and ireland. in many countries, pgd is permitted under very stringent conditions for medical use only, as is the case in france, switzerland, italy and the united kingdom. whilst pgd in italy and switzerland is only permitted under certain circumstances, there is no clear set of specifications under which pgd can be carried out, and selection of embryos based on sex is not permitted. in france and the uk, regulations are much more detailed, with dedicated agencies setting out framework for pgd. selection based on sex is permitted under certain circumstances, and genetic disorders for which pgd is permitted are detailed by the countries' respective agencies. in contrast, the united states federal law does not regulate pgd, with no dedicated agencies specifying regulatory framework by which healthcare professionals must abide. elective sex selection is permitted, accounting for around 9% of all pgd cases in the u.s., as is selection for desired conditions such as deafness or dwarfism. human germline engineering human germline engineering is a process in which the human genome is edited within a germ cell, such as a sperm cell or oocyte (causing heritable changes), or in the zygote or embryo following fertilization. germline engineering results in changes in the genome being incorporated into every cell in the body of the offspring (or of the individual following embryonic germline engineering). this process differs from somatic cell engineering, which does not result in heritable changes. most human germline editing is performed on individual cells and non-viable embryos, which are destroyed at a very early stage of development. in november 2018, however, a chinese scientist, he jiankui, announced that he had created the first human germline genetically edited babies. genetic engineering relies on a knowledge of human genetic information, made possible by research such as the human genome project, which identified the position and function of all the genes in the human genome. as of 2019, high-throughput sequencing methods allow genome sequencing to be conducted very rapidly, making the technology widely available to researchers. germline modification is typically accomplished through techniques which incorporate a new gene into the genome of the embryo or germ cell in a specific location. this can be achieved by introducing the desired dna directly to the cell for it to be incorporated, or by replacing a gene with one of interest. these techniques can also be used to remove or disrupt unwanted genes, such as ones containing mutated sequences. whilst germline engineering has mostly been performed in mammals and other animals, research on human cells in vitro is becoming more common. most commonly used in human cells are germline gene therapy and the engineered nuclease system crispr/cas9. germline gene modification gene therapy is the delivery of a nucleic acid (usually dna or rna) into a cell as a pharmaceutical agent to treat disease. most commonly it is carried out using a vector, which transports the nucleic acid (usually dna encoding a therapeutic gene) into the target cell. a vector can transduce a desired copy of a gene into a specific location to be expressed as required. alternatively, a transgene can be inserted to deliberately disrupt an unwanted or mutated gene, preventing transcription and translation of the faulty gene products to avoid a disease phenotype. gene therapy in patients is typically carried out on somatic cells in order to treat conditions such as some leukaemias and vascular diseases. human germline gene therapy in contrast is restricted to in vitro experiments in some countries, whilst others prohibited it entirely, including australia, canada, germany and switzerland. whilst the national institutes of health in the us does not currently allow in utero germline gene transfer clinical trials, in vitro trials are permitted. the nih guidelines state that further studies are required regarding the safety of gene transfer protocols before in utero research is considered, requiring current studies to provide demonstrable efficacy of the techniques in the laboratory. research of this sort is currently using non-viable embryos to investigate the efficacy of germline gene therapy in treatment of disorders such as inherited mitochondrial diseases. gene transfer to cells is usually by vector delivery. vectors are typically divided into two classes – viral and non-viral. viral vectors viruses infect cells by transducing their genetic material into a host's cell, using the host's cellular machinery to generate viral proteins needed for replication and proliferation. by modifying viruses and loading them with the therapeutic dna or rna of interest, it is possible to use these as a vector to provide delivery of the desired gene into the cell. retroviruses are some of the most commonly used viral vectors, as they not only introduce their genetic material into the host cell, but also copy it into the host's genome. in the context of gene therapy, this allows permanent integration of the gene of interest into the patient's own dna, providing longer lasting effects. viral vectors work efficiently and are mostly safe but present with some complications, contributing to the stringency of regulation on gene therapy. despite partial inactivation of viral vectors in gene therapy research, they can still be immunogenic and elicit an immune response. this can impede viral delivery of the gene of interest, as well as cause complications for the patient themselves when used clinically, especially in those who already have a serious genetic illness. another difficulty is the possibility that some viruses will randomly integrate their nucleic acids into the genome, which can interrupt gene function and generate new mutations. this is a significant concern when considering germline gene therapy, due to the potential to generate new mutations in the embryo or offspring. non-viral vectors non-viral methods of nucleic acid transfection involved injecting a naked dna plasmid into cell for incorporation into the genome. this method used to be relatively ineffective with low frequency of integration, however, efficiency has since greatly improved, using methods to enhance the delivery of the gene of interest into cells. furthermore, non-viral vectors are simple to produce on a large scale and are not highly immunogenic. some non-viral methods are detailed below: electroporation is a technique in which high voltage pulses are used to carry dna into the target cell across the membrane. the method is believed to function due to the formation of pores across the membrane, but although these are temporary, electroporation results in a high rate of cell death which has limited its use. an improved version of this technology, electron-avalanche transfection, has since been developed, which involves shorter (microsecond) high voltage pulses which result in more effective dna integration and less cellular damage. the gene gun is a physical method of dna transfection, where a dna plasmid is loaded onto a particle of heavy metal (usually gold) and loaded onto the 'gun'. the device generates a force to penetrate the cell membrane, allowing the dna to enter whilst retaining the metal particle. oligonucleotides are used as chemical vectors for gene therapy, often used to disrupt mutated dna sequences to prevent their expression. disruption in this way can be achieved by introduction of small rna molecules, called sirna, which signal cellular machinery to cleave the unwanted mrna sequences to prevent their transcription. another method