Designer baby

A designer baby is an embryo or fetus whose genetic makeup has been intentionally selected or altered, often to exclude a particular gene or to remove genes associated with disease, to achieve desired traits. This process usually involves preimplantation genetic diagnosis, which analyzes multiple human embryos to identify genes associated with specific diseases and characteristics, then selecting embryos that have the desired genetic makeup. While screening for single genes is commonly practiced, advancements in polygenic screening are becoming more prominent, though only a few companies currently offer it. This technique uses an algorithm to aggregate the estimated effects of numerous genetic variants tied to an individual's risk for a particular condition or trait. Other methods of altering a baby's genetic information involve directly editing the genome before birth, using technologies such as CRISPR. A controversial example of this can be seen in the 2018 case involving Chinese twins Lulu and Nana, which had their genomes edited to resist HIV infection, sparking widespread criticism and legal debates.
This highlights the implications of germline engineering, which involves introducing the desired genetic material into the embryo or parental germ cells. This process is typically prohibited by law, however, regulations vary globally. Editing embryos in this manner can result in genetic changes that are passed down to future generations, raising significant controversy and ethical concerns. While some scientists advocate for its use in treating genetic diseases, others warn that it could lead to misuse for non-medical purposes, such as cosmetic enhancements and modification of human traits.

Pre-implantation genetic diagnosis

Pre-implantation genetic diagnosis is a procedure in which embryos are screened prior to implantation. The technique is used alongside in vitro fertilisation to obtain embryos for evaluation of the genome – alternatively, oocytes 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. 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 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

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, 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, 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 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 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 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.

Polygenic risk score (PRS) screening

In the 2020s, companies such as Orchid Bioscience began offering polygenic risk scores analysis for embryos during IVF. PRS estimates the likelihood of complex traits, such as height and intelligence, or diseases like diabetes, by summarizing data from thousands of genetic markers. However, many geneticists and bioethicists argue that PRS predictions lack clinical validity and promote eugenic practices that can prioritize socially desirable characteristics. They believe this approach risks reinforcing societal biases that may not be realistic and limits the autonomy and identity of the child as it restricts their life within a framework of genetic predictions. A 2021 study found that PRS explains only 5-10% of variance in educational attainment, highlighting its limited predictive ability.

Pre-implantation Genetic Testing

Based on the specific analysis conducted:
PGT-M is a technique used during IVF to detect hereditary diseases caused by mutations or alterations of the DNA sequence with a single gene.
PGT-A : It is used to diagnose numerical abnormalities.

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, 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. 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

is the delivery of a nucleic acid into a cell as a pharmaceutical agent to treat disease. Most commonly it is carried out using a vector, which transports the nucleic acid 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.