A designer baby is a baby whose
genetic makeup has been selected or altered, often to not include a particular
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
or to remove genes associated with disease. This process usually involves analysing a wide range of human
embryos
An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sper ...
to identify genes associated with particular
disease
A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
s and characteristics, and selecting embryos that have the desired genetic makeup; a process known as
preimplantation genetic diagnosis
Preimplantation genetic diagnosis (PGD or PIGD) is the genetic profiling of embryos prior to implantation (as a form of embryo profiling), and sometimes even of oocytes prior to fertilization. PGD is considered in a similar fashion to prenatal ...
. Screening for single genes is commonly practiced, and polygenic screening is offered by a few companies. Other potential 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
The He Jiankui affair is a scientific and Bioethics, bioethical controversy concerning the use of genome editing following its first use on humans by Chinese scientist He Jiankui, who edited the genomes of human embryos in 2018. He became widel ...
were edited as embryos, causing widespread criticism.
Genetically altered embryos can be achieved by introducing the desired genetic material into the embryo itself, or into the
sperm
Sperm is the male reproductive cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm with a tail known as a flagellum, whi ...
and/or
egg
An egg is an organic vessel grown by an animal to carry a possibly fertilized egg cell (a zygote) and to incubate from it an embryo within the egg until the embryo has become an animal fetus that can survive on its own, at which point the a ...
cells of the parents; either by
delivering the desired genes directly into the cell or using the gene-editing technology. This process is known as
germline engineering
Assisted reproductive technology (ART) includes medical procedures used primarily to address infertility. This subject involves procedures such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), cryopreservation of gametes o ...
and performing this on embryos that will be brought to term is not typically permitted 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, some have raised concerns that this could be translated into using the technology for cosmetic means and
enhancement of human traits, with implications for the wider society.
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
Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...
. 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
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitos ...
or disease-related
alleles
An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution.
::"The chro ...
and selection against them. It is especially useful in embryos from parents where one or both carry a
heritable disease
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
. 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
Haemophilia, or hemophilia (), is a mostly inherited genetic disorder that impairs the body's ability to make blood clots, a process needed to stop bleeding. This results in people bleeding for a longer time after an injury, easy bruising, ...
). Infants born with traits selected following PGD are sometimes considered to be designer babies.
One application of PGD is the selection of '
saviour siblings
A savior baby or savior sibling is a child who is conceived in order to provide a stem cell transplant to a sibling that is affected with a fatal disease, such as cancer or Fanconi anemia, that can best be treated by hematopoietic stem cell transp ...
', 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
![PGD process](https://upload.wikimedia.org/wikipedia/commons/8/85/PGD_process.png)
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 Controlled ovarian hyperstimulation is a technique used in assisted reproduction involving the use of fertility medications to induce ovulation by multiple ovarian follicles. These multiple follicles can be taken out by oocyte retrieval (egg collect ...
(COH), which involves fertility treatments to induce production of multiple oocytes. After harvesting the oocytes, they are fertilised ''
in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
'', either during incubation with multiple sperm cells in culture, or ''via''
intracytoplasmic sperm injection
Intracytoplasmic sperm injection (ICSI ) is an in vitro fertilization (IVF) procedure in which a single sperm cell is injected directly into the cytoplasm of an egg. This technique is used in order to prepare the gametes for the obtention of emb ...
(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
In biology, a blastomere is a type of cell produced by cell division (cleavage) of the zygote after fertilization; blastomeres are an essential part of blastula formation, and blastocyst formation in mammals.
Human blastomere characteristics
In h ...
or
blastocyst
The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the ''embryoblast'' which subsequently forms the embryo, and an outer layer of trophoblast cells called the t ...
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
The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) t ...
(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
Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. O ...
.
Another screening technique,
fluorescent ''in situ'' hybridisation (FISH) uses fluorescent probes which specifically bind to highly
complementary sequences
: ''For complementary sequences in biology, see complementarity (molecular biology). For integer sequences with complementary sets of members see Lambek–Moser theorem.''
In applied mathematics, complementary sequences (CS) are pairs of sequences ...
on
chromosomes
A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
, which can then be identified using
fluorescence microscopy
A fluorescence microscope is an optical microscope that uses fluorescence instead of, or in addition to, scattering, reflection, and attenuation or absorption, to study the properties of organic or inorganic substances. "Fluorescence microsc ...
.
FISH is often used when screening for chromosomal abnormalities such as
aneuploidy
Aneuploidy is the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes instead of the usual 46. It does not include a difference of one or more complete sets of chromosomes. A cell with any ...
, making it a useful tool when screening for disorders such as
Down syndrome
Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is usually associated with physical growth delays, mild to moderate intellectual dis ...
.
Following the screening, embryos with the desired trait (or lacking an undesired trait such as a mutation) are transferred into the mother's
uterus
The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The uter ...
, then allowed to
develop naturally.
Regulation
PGD regulation is determined by individual countries' governments, with some prohibiting its use entirely, including in
Austria
Austria, , bar, Östareich officially the Republic of Austria, is a country in the southern part of Central Europe, lying in the Eastern Alps. It is a federation of nine states, one of which is the capital, Vienna, the most populous ...
,
China
China, officially the People's Republic of China (PRC), is a country in East Asia. It is the world's most populous country, with a population exceeding 1.4 billion, slightly ahead of India. China spans the equivalent of five time zones and ...
, and
Ireland
Ireland ( ; ga, Éire ; Ulster Scots dialect, Ulster-Scots: ) is an island in the Atlantic Ocean, North Atlantic Ocean, in Northwestern Europe, north-western Europe. It is separated from Great Britain to its east by the North Channel (Grea ...
.
In many countries, PGD is permitted under very stringent conditions for medical use only, as is the case in
France
France (), officially the French Republic ( ), is a country primarily located in Western Europe. It also comprises of Overseas France, overseas regions and territories in the Americas and the Atlantic Ocean, Atlantic, Pacific Ocean, Pac ...
,
Switzerland
). Swiss law does not designate a ''capital'' as such, but the federal parliament and government are installed in Bern, while other federal institutions, such as the federal courts, are in other cities (Bellinzona, Lausanne, Luzern, Neuchâtel ...
,
Italy
Italy ( it, Italia ), officially the Italian Republic, ) or the Republic of Italy, is a country in Southern Europe. It is located in the middle of the Mediterranean Sea, and its territory largely coincides with the homonymous geographical re ...
and the
United Kingdom
The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Europe, off the north-western coast of the continental mainland. It comprises England, Scotland, Wales and North ...
.
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
The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...
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
Deafness has varying definitions in cultural and medical contexts. In medical contexts, the meaning of deafness is hearing loss that precludes a person from understanding spoken language, an audiological condition. In this context it is written ...
or
dwarfism
Dwarfism is a condition wherein an organism is exceptionally small, and mostly occurs in the animal kingdom. In humans, it is sometimes defined as an adult height of less than , regardless of sex; the average adult height among people with dw ...
.
Human germline engineering
Human germline engineering is a process in which the human genome is edited within a
germ cell
Germ or germs may refer to:
Science
* Germ (microorganism), an informal word for a pathogen
* Germ cell, cell that gives rise to the gametes of an organism that reproduces sexually
* Germ layer, a primary layer of cells that forms during embry ...
, such as a sperm cell or oocyte (causing heritable changes), or in the
zygote
A zygote (, ) is a eukaryotic cell formed by a fertilization event between two gametes. The zygote's genome is a combination of the DNA in each gamete, and contains all of the genetic information of a new individual organism.
In multicellula ...
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
A somatic cell (from Ancient Greek σῶμα ''sôma'', meaning "body"), or vegetal cell, is any biological cell forming the body of a multicellular organism other than a gamete, germ cell, gametocyte or undifferentiated stem cell. Such cells compo ...
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
He Jiankui (; ; born 1984) is a Chinese biophysics researcher who was an associate professor in the Department of Biology of the Southern University of Science and Technology (SUSTech) in Shenzhen, China. Earning his Ph.D. from Rice University ...
, 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
The Human Genome Project (HGP) was an international scientific research project with the goal of determining the base pairs that make up human DNA, and of identifying, mapping and sequencing all of the genes of the human genome from both a ...
, which identified the position and function of all the genes in the human genome.
As of 2019,
high-throughput sequencing
DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, guanine, cytosine, and thymine. The ...
methods allow
genome sequencing
Whole genome sequencing (WGS), also known as full genome sequencing, complete genome sequencing, or entire genome sequencing, is the process of determining the entirety, or nearly the entirety, of the DNA sequence of an organism's genome at a ...
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
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
and other animals, research on human cells ''in vitro'' is becoming more common. Most commonly used in human cells are
germline gene therapy
Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...
and the engineered nuclease system
CRISPR/Cas9
Cas9 (CRISPR associated protein 9, formerly called Cas5, Csn1, or Csx12) is a 160 kilodalton protein which plays a vital role in the immunological defense of certain bacteria against DNA viruses and plasmids, and is heavily utilized in genetic e ...
.
Germline gene modification
Gene therapy
Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...
is the delivery of a
nucleic acid
Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main cl ...
(usually DNA or
RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
) into a cell as a pharmaceutical agent to treat disease.
Most commonly it is carried out using a
vector
Vector most often refers to:
*Euclidean vector, a quantity with a magnitude and a direction
*Vector (epidemiology), an agent that carries and transmits an infectious pathogen into another living organism
Vector may also refer to:
Mathematic ...
, 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
A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the ...
can be inserted to deliberately disrupt an unwanted or mutated gene, preventing
transcription
Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including:
Genetics
* Transcription (biology), the copying of DNA into RNA, the fir ...
and
translation
Translation is the communication of the Meaning (linguistic), meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The ...
of the faulty gene products to avoid a disease
phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...
.
Gene therapy in patients is typically carried out on somatic cells in order to treat conditions such as some
leukaemias and
vascular diseases
Vascular disease is a class of diseases of the blood vessels – the arteries and veins of the circulatory system of the body. Vascular disease is a subgroup of cardiovascular disease. Disorders in this vast network of blood vessels can cause a ...
.
Human germline gene therapy in contrast is restricted to ''in vitro'' experiments in some countries, whilst others prohibited it entirely, including
Australia
Australia, officially the Commonwealth of Australia, is a Sovereign state, sovereign country comprising the mainland of the Australia (continent), Australian continent, the island of Tasmania, and numerous List of islands of Australia, sma ...
,
Canada
Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by tot ...
,
Germany
Germany,, officially the Federal Republic of Germany, is a country in Central Europe. It is the second most populous country in Europe after Russia, and the most populous member state of the European Union. Germany is situated betwe ...
and Switzerland.
Whilst the
National Institutes of Health
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
in the US does not currently allow ''
in utero
''In Utero'' is the third and final studio album by American rock band Nirvana. It was released on September 21, 1993, by DGC Records. After breaking into the mainstream with their second album, ''Nevermind'' (1991), Nirvana hired Steve Albini t ...
'' 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
Mitochondrial disease is a group of disorders caused by mitochondrial dysfunction. Mitochondria are the organelles that generate energy for the cell and are found in every cell of the human body except red blood cells. They convert the energy of ...
.
Gene transfer to cells is usually by vector delivery. Vectors are typically divided into two classes –
viral and
non-viral.
Viral vectors
Viruses
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's 1 ...
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
A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase e ...
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
Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted:
* Wanted immunogenicity typically relates to vaccines, where the injectio ...
and elicit an
immune response
An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...
. 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
Transfection is the process of deliberately introducing naked or purified nucleic acids into eukaryotic cells. It may also refer to other methods and cell types, although other terms are often preferred: "transformation" is typically used to desc ...
involved injecting a naked DNA
plasmid
A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...
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
Electroporation, or electropermeabilization, is a microbiology technique in which an electrical field is applied to cells in order to increase the permeability of the cell membrane, allowing chemicals, drugs, electrode arrays or DNA to be introdu ...
is a technique in which high voltage pulses are used to carry DNA into the target cell across the
membrane
A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. B ...
. 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
Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, as in programmed cell death, or may result from factors such as dis ...
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
In genetic engineering, a gene gun or biolistic particle delivery system is a device used to deliver exogenous DNA (transgenes), RNA, or protein to cells. By coating particles of a heavy metal with a gene of interest and firing these micro-projec ...
is a physical method of DNA transfection, where a DNA plasmid is loaded onto a particle of
heavy metal (usually
gold
Gold is a chemical element with the symbol Au (from la, aurum) and atomic number 79. This makes it one of the higher atomic number elements that occur naturally. It is a bright, slightly orange-yellow, dense, soft, malleable, and ductile met ...
) 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
Oligonucleotides are short DNA or RNA molecules, oligomers, that have a wide range of applications in genetic testing, research, and forensics. Commonly made in the laboratory by solid-phase chemical synthesis, these small bits of nucleic acids c ...
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
Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA at first non-coding RNA molecules, typically 20-24 (normally 21) base pairs in length, similar to miRNA, and operating wi ...
, which signal cellular machinery to cleave the unwanted
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein.
mRNA is ...
sequences to prevent their transcription. Another method utilises double-stranded oligonucleotides, which bind
transcription factors
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The func ...
required for transcription of the target gene. By competitively binding these transcription factors, the oligonucleotides can prevent the gene's expression.
ZFNs
Zinc-finger nucleases (ZFNs) are enzymes generated by fusing a zinc finger DNA-binding domain to a DNA-cleavage domain. Zinc finger recognizes between 9 and 18 bases of sequence. Thus by mixing those modules, it becomes easier to target any sequence researchers wish to alter ideally within complex genomes. A ZFN is a
macromolecular
A macromolecule is a very large molecule important to biophysical processes, such as a protein or nucleic acid. It is composed of thousands of covalently bonded atoms. Many macromolecules are polymers of smaller molecules called monomers. The ...
complex formed by monomers in which each subunit contains a zinc domain and a
FokI endonuclease domain. The FokI domains must dimerize for activities, thus narrowing target area by ensuring that two close DNA-binding events occurs.
The resulting cleavage event enables most genome-editing technologies to work. After a break is created, the cell seeks to repair it.
* A method is
NHEJ
Non-homologous end joining (NHEJ) is a pathway that repairs double-strand breaks in DNA. NHEJ is referred to as "non-homologous" because the break ends are directly ligated without the need for a homologous template, in contrast to homology direc ...
, in which the cell polishes the two ends of broken DNA and seals them back together, often producing a frame shift.
* An alternative method is
homology-directed repairs. The cell tries to fix the damage by using a copy of the sequence as a backup. By supplying their own template, researcher can have the system to insert a desired sequence instead.
The success of using ZFNs in gene therapy depends on the insertion of genes to the chromosomal target area without causing damage to the cell. Custom ZFNs offer an option in human cells for gene correction.
TALENs
There is a method called
TALENs
Transcription activator-like effector nucleases (TALEN) are restriction enzymes that can be engineered to cut specific sequences of DNA. They are made by fusing a TAL effector DNA-binding domain to a DNA cleavage domain (a nuclease which cuts DN ...
that targets singular nucleotides. TALENs stand for transcription activator-like effector nucleases. TALENs are made by
TAL effector DNA-binding domain to a DNA cleavage domain. All these methods work by as the TALENs are arranged. TALENs are "built from arrays of 33-35 amino acid modules…by assembling those arrays…researchers can target any sequence they like".
This event is referred as Repeat Variable Diresidue (RVD). The relationship between the amino acids enables researchers to engineer a specific DNA domain. The TALEN enzymes are designed to remove specific parts of the DNA strands and replace the section; which enables edits to be made. TALENs can be used to edit genomes using
non-homologous end joining
Non-homologous end joining (NHEJ) is a pathway that repairs double-strand breaks in DNA. NHEJ is referred to as "non-homologous" because the break ends are directly ligated without the need for a homologous template, in contrast to homology direct ...
(NHEJ) and
homology directed repair
Homology-directed repair (HDR) is a mechanism in cells to repair double-strand DNA lesions. The most common form of HDR is homologous recombination. The HDR mechanism can only be used by the cell when there is a homologous piece of DNA presen ...
.
CRISPR/Cas9
![GRNA-Cas9-colourfriendly](https://upload.wikimedia.org/wikipedia/commons/5/53/GRNA-Cas9-colourfriendly.png)
The CRISPR/Cas9 system (
CRISPR
CRISPR () (an acronym for clustered regularly interspaced short palindromic repeats) is a family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea. These sequences are derived from DNA fragments of bacte ...
– Clustered Regularly Interspaced Short Palindromic Repeats,
Cas9
Cas9 (CRISPR associated protein 9, formerly called Cas5, Csn1, or Csx12) is a 160 kilodalton protein which plays a vital role in the immunological defense of certain bacteria against DNA viruses and plasmids, and is heavily utilized in genetic e ...
– CRISPR-associated protein 9) is a genome editing technology based on the
bacterial
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
antiviral CRISPR/Cas system. The bacterial system has evolved to recognize viral nucleic acid sequences and cut these sequences upon recognition, damaging infecting viruses. The gene editing technology uses a simplified version of this process, manipulating the components of the bacterial system to allow location-specific gene editing.
The CRISPR/Cas9 system broadly consists of two major components – the Cas9
nuclease
A nuclease (also archaically known as nucleodepolymerase or polynucleotidase) is an enzyme capable of cleaving the phosphodiester bonds between nucleotides of nucleic acids. Nucleases variously effect single and double stranded breaks in their ta ...
and a
guide RNA
A guide RNA (gRNA) is a piece of RNA that functions as a guide for RNA- or DNA-targeting enzymes, with which it forms complexes. Very often these enzymes will delete, insert or otherwise alter the targeted RNA or DNA. They occur naturally, serv ...
(gRNA). The gRNA contains a Cas-binding sequence and a ~20
nucleotide
Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...
spacer sequence, which is specific and complementary to the target sequence on the DNA of interest. Editing specificity can therefore be changed by modifying this spacer sequence.
![DNA Repair-colourfriendly](https://upload.wikimedia.org/wikipedia/commons/0/04/DNA_Repair-colourfriendly.png)
Upon system delivery to a cell, Cas9 and the gRNA bind, forming a
ribonucleoprotein
Nucleoproteins are proteins conjugated with nucleic acids (either DNA or RNA). Typical nucleoproteins include ribosomes, nucleosomes and viral nucleocapsid proteins.
Structures
Nucleoproteins tend to be positively charged, facilitating in ...
complex. This causes a
conformational change
In biochemistry, a conformational change is a change in the shape of a macromolecule, often induced by environmental factors.
A macromolecule is usually flexible and dynamic. Its shape can change in response to changes in its environment or oth ...
in Cas9, allowing it to cleave DNA if the gRNA spacer sequence binds with sufficient
homology
Homology may refer to:
Sciences
Biology
*Homology (biology), any characteristic of biological organisms that is derived from a common ancestor
* Sequence homology, biological homology between DNA, RNA, or protein sequences
*Homologous chrom ...
to a particular sequence in the host genome.
When the gRNA binds to the target sequence, Cas will cleave the
locus
Locus (plural loci) is Latin for "place". It may refer to:
Entertainment
* Locus (comics), a Marvel Comics mutant villainess, a member of the Mutant Liberation Front
* ''Locus'' (magazine), science fiction and fantasy magazine
** ''Locus Award' ...
, causing a
double-strand break
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA dam ...
(DSB).
The resulting DSB can be
repaired by one of two mechanisms –
*
Non-Homologous End Joining
Non-homologous end joining (NHEJ) is a pathway that repairs double-strand breaks in DNA. NHEJ is referred to as "non-homologous" because the break ends are directly ligated without the need for a homologous template, in contrast to homology direct ...
(NHEJ) - an efficient but error-prone mechanism, which often introduces insertions and deletions (
indels
Indel is a molecular biology term for an insertion or deletion of bases in the genome of an organism. It is classified among small genetic variations, measuring from 1 to 10 000 base pairs in length, including insertion and deletion events that ...
) at the DSB site. This means it is often used in
knockout
A knockout (abbreviated to KO or K.O.) is a fight-ending, winning criterion in several full-contact combat sports, such as boxing, kickboxing, muay thai, mixed martial arts, karate, some forms of taekwondo and other sports involving striking, a ...
experiments to disrupt genes and introduce loss of function mutations.
*
Homology Directed Repair
Homology-directed repair (HDR) is a mechanism in cells to repair double-strand DNA lesions. The most common form of HDR is homologous recombination. The HDR mechanism can only be used by the cell when there is a homologous piece of DNA presen ...
(HDR) - a less efficient but high-fidelity process which is used to introduce precise modifications into the target sequence. The process requires adding a DNA repair template including a desired sequence, which the cell's machinery uses to repair the DSB, incorporating the sequence of interest into the genome.
Since NHEJ is more efficient than HDR, most DSBs will be repaired ''via'' NHEJ, introducing gene knockouts. To increase frequency of HDR, inhibiting genes associated with NHEJ and performing the process in particular
cell cycle
The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...
phases (primarily
S and
G2) appear effective.
CRISPR/Cas9 is an effective way of manipulating the genome ''
in vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
'' in animals as well as in human cells ''in vitro'', but some issues with the efficiency of delivery and editing mean that it is not considered safe for use in viable human embryos or the body's germ cells. As well as the higher efficiency of NHEJ making inadvertent knockouts likely, CRISPR can introduce DSBs to unintended parts of the genome, called off-target effects.
These arise due to the spacer sequence of the gRNA conferring sufficient sequence homology to random loci in the genome, which can introduce random mutations throughout. If performed in germline cells, mutations could be introduced to all the cells of a developing embryo.
There are developments to prevent unintended consequences otherwise known as off-target effects due to gene editing.
There is a race to develop new gene editing technologies that prevent off-target effects from occurring with some of the technologies being known as biased off-target detection, and Anti-CRISPR Proteins.
For biased off-target effects detection, there are several tools to predict the locations where off-target effects may take place.
Within the technology of biased off-target effects detection, there are two main models, Alignment Based Models that involve having the sequences of gRNA being aligned with sequences of genome, after which then the off-target locations are predicted.
The second model is known as the Scoring-Based Model where each piece of gRNA is scored for their off-target effects in accordance with their positioning.
Regulation on CRISPR use
In 2015, the International Summit on Human Gene Editing was held in
Washington D.C.
)
, image_skyline =
, image_caption = Clockwise from top left: the Washington Monument and Lincoln Memorial on the National Mall, United States Capitol, Logan Circle, Jefferson Memorial, White House, Adams Morgan, Na ...
, hosted by scientists from China, the UK and the U.S.. The summit concluded that genome editing of somatic cells using CRISPR and other genome editing tools would be allowed to proceed under
FDA
The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
regulations, but human germline engineering would not be pursued.
In February 2016, scientists at the
Francis Crick Institute
The Francis Crick Institute (formerly the UK Centre for Medical Research and Innovation) is a biomedical research centre in London, which was established in 2010 and opened in 2016. The institute is a partnership between Cancer Research UK, Impe ...
in
London
London is the capital and largest city of England and the United Kingdom, with a population of just under 9 million. It stands on the River Thames in south-east England at the head of a estuary down to the North Sea, and has been a majo ...
were given a license permitting them to edit human embryos using CRISPR to investigate early development.
Regulations were imposed to prevent the researchers from implanting the embryos and to ensure experiments were stopped and embryos destroyed after seven days.
In November 2018, Chinese scientist
He Jiankui
He Jiankui (; ; born 1984) is a Chinese biophysics researcher who was an associate professor in the Department of Biology of the Southern University of Science and Technology (SUSTech) in Shenzhen, China. Earning his Ph.D. from Rice University ...
announced that he had performed the first germline engineering on viable humans embryos, which have since been brought to term.
The research claims received significant criticism, and Chinese authorities suspended He's research activity.
Following the event, scientists and government bodies have called for more stringent regulations to be imposed on the use of CRISPR technology in embryos, with some calling for a global
moratorium on germline genetic engineering. Chinese authorities have announced stricter controls will be imposed, with
Communist Party
A communist party is a political party that seeks to realize the socio-economic goals of communism. The term ''communist party'' was popularized by the title of ''The Manifesto of the Communist Party'' (1848) by Karl Marx and Friedrich Engels. A ...
general secretary
Xi Jinping
Xi Jinping ( ; ; ; born 15 June 1953) is a Chinese politician who has served as the general secretary of the Chinese Communist Party (CCP) and chairman of the Central Military Commission (CMC), and thus as the paramount leader of China, s ...
and
government
A government is the system or group of people governing an organized community, generally a state.
In the case of its broad associative definition, government normally consists of legislature, executive, and judiciary. Government is a ...
premier
Li Keqiang
Li Keqiang (born 1 July 1955) is a Chinese politician who is the outgoing premier of China. An economist by profession, Li is head of China's executive branch as well as one of the leading figures behind China's Financial and Economic Affai ...
calling for new gene-editing legislations to be introduced.
As of January 2020, germline genetic alterations are prohibited in 24 countries by law and also in 9 other countries by their guidelines. The
Council of Europe
The Council of Europe (CoE; french: Conseil de l'Europe, ) is an international organisation founded in the wake of World War II to uphold European Convention on Human Rights, human rights, democracy and the Law in Europe, rule of law in Europe. ...
's Convention on Human Rights and Biomedicine, also known as the Oviedo Convention, has stated in its article 13 "Interventions on the human genome" as follows: "An intervention seeking to modify the human genome may only be undertaken for preventive, diagnostic or therapeutic purposes and only if its aim is not to introduce any modification in the genome of any descendants". Nonetheless, wide public debate has emerged, targeting the fact that the Oviedo Convention Article 13 should be revisited and renewed, especially due to the fact that it was constructed in 1997 and may be out of date, given recent technological advancements in the field of genetic engineering.
Lulu and Nana controversy
![He Jiankui at Second International Summit on Human Genome Editing (cropped)](https://upload.wikimedia.org/wikipedia/commons/9/95/He_Jiankui_at_Second_International_Summit_on_Human_Genome_Editing_%28cropped%29.jpg)
The Lulu and Nana controversy refers to the two Chinese twin girls born in November 2018, who had been genetically modified as embryos by the Chinese scientist He Jiankui.
The twins are believed to be the first genetically modified babies. The girls' parents had participated in a clinical project run by He, which involved IVF, PGD and genome editing procedures in an attempt to edit the gene
CCR5
C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines.
In humans, the ''CCR5'' gene that encodes the CCR5 pro ...
. CCR5 encodes a protein used by
HIV
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
to enter host cells, so by introducing a specific mutation into the gene
CCR5 Δ32 He claimed that the process would confer
innate resistance to HIV
A small proportion of humans show partial or apparently complete innate resistance to HIV, the virus that causes AIDS. The main mechanism is a mutation of the gene encoding CCR5, which acts as a co-receptor for HIV. It is estimated that the propor ...
.
The project run by He recruited couples wanting children where the man was
HIV-positive
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause AIDS, acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the ...
and the woman uninfected. During the project, He performed IVF with sperm and eggs from the couples and then introduced the CCR5 Δ32 mutation into the genomes of the embryos using CRISPR/Cas9. He then used PGD on the edited embryos during which he sequenced biopsied cells to identify whether the mutation had been successfully introduced. He reported some
mosaicism
Mosaicism or genetic mosaicism is a condition in multicellular organisms in which a single organism possesses more than one genetic line as the result of genetic mutation. This means that various genetic lines resulted from a single fertilized e ...
in the embryos, whereby the mutation had integrated into some cells but not all, suggesting the offspring would not be entirely protected against HIV.
He claimed that during the PGD and throughout the pregnancy,
foetal DNA was sequenced to check for off-target errors introduced by the CRISPR/Cas9 technology, however the NIH released a statement in which they announced "the possibility of damaging off-target effects has not been satisfactorily explored".
The girls were born in early November 2018, and were reported by He to be healthy.
His research was conducted in secret until November 2018, when documents were posted on the Chinese clinical trials registry and ''
MIT Technology Review
''MIT Technology Review'' is a bimonthly magazine wholly owned by the Massachusetts Institute of Technology, and editorially independent of the university. It was founded in 1899 as ''The Technology Review'', and was re-launched without "The" in ...
'' published a story about the project.
Following this, He was interviewed by the ''
Associated Press
The Associated Press (AP) is an American non-profit news agency headquartered in New York City. Founded in 1846, it operates as a cooperative, unincorporated association. It produces news reports that are distributed to its members, U.S. newspa ...
'' and presented his work on 27 November and the Second International Human Genome Editing Summit which was held in
Hong Kong
Hong Kong ( (US) or (UK); , ), officially the Hong Kong Special Administrative Region of the People's Republic of China ( abbr. Hong Kong SAR or HKSAR), is a city and special administrative region of China on the eastern Pearl River Delt ...
.
Although the information available about this experiment is relatively limited, it is deemed that the scientist erred against many ethical, social and moral rules but also China's guidelines and regulations, which prohibited germ-line genetic modifications in human embryos, while conducting this trial.
From a technological point of view, the CRISPR/Cas9 technique is one of the most precise and least expensive methods of gene modification to this day, whereas there are still a number of limitations that keep the technique from being labelled as safe and efficient.
During the First International Summit on Human Gene Editing in 2015 the participants agreed that a halt must be set on germline genetic alterations in clinical settings unless and until: "(1) the relevant safety and efficacy issues have been resolved, based on appropriate understanding and balancing of risks, potential benefits, and alternatives, and (2) there is broad societal consensus about the appropriateness of the proposed application".
However, during the second International Summit in 2018 the topic was once again brought up by stating: "Progress over the last three years and the discussions at the current summit, however, suggest that it is time to define a rigorous, responsible translational pathway toward such trials".
Inciting that the ethical and legal aspects should indeed be revisited G. Daley, representative of the summit's management and Dean of Harvard Medical School depicted Dr. He's experiment as "a wrong turn on the right path".
The experiment was met with widespread criticism and was very controversial, globally as well as in China.
Several
bioethicists
Bioethics is both a field of study and professional practice, interested in ethical issues related to health (primarily focused on the human, but also increasingly includes animal ethics), including those emerging from advances in biology, med ...
, researchers and medical professionals have released statements condemning the research, including
Nobel laureate
The Nobel Prizes ( sv, Nobelpriset, no, Nobelprisen) are awarded annually by the Royal Swedish Academy of Sciences, the Swedish Academy, the Karolinska Institutet, and the Norwegian Nobel Committee to individuals and organizations who make out ...
David Baltimore
David Baltimore (born March 7, 1938) is an American biologist, university administrator, and 1975 Nobel laureate in Physiology or Medicine. He is President Emeritus and Distinguished Professor of Biology at the California Institute of Technolo ...
who deemed the work "irresponsible" and one pioneer of the CRISPR/Cas9 technology, biochemist
Jennifer Doudna
Jennifer Anne Doudna (; born February 19, 1964) is an American biochemist who has done pioneering work in CRISPR gene editing, and made other fundamental contributions in biochemistry and genetics. Doudna was one of the first women to share a ...
at
University of California, Berkeley
The University of California, Berkeley (UC Berkeley, Berkeley, Cal, or California) is a public land-grant research university in Berkeley, California. Established in 1868 as the University of California, it is the state's first land-grant u ...
.
The director of the NIH,
Francis S. Collins stated that the "medical necessity for inactivation of CCR5 in these infants is utterly unconvincing" and condemned He Jiankui and his research team for 'irresponsible work'.
Other scientists, including
geneticist
A geneticist is a biologist or physician who studies genetics, the science of genes, heredity, and variation of organisms. A geneticist can be employed as a scientist or a lecturer. Geneticists may perform general research on genetic processe ...
George Church of
Harvard University
Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher le ...
suggested gene editing for disease resistance was "justifiable" but expressed reservations regarding the conduct of He's work.
The Safe Genes program by DARPA has the goal to protect soldiers against gene editing war tactics.
They receive information from ethical experts to better predict and understand future and current potential gene editing issues.
The
World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
has launched a global registry to track research on human genome editing, after a call to halt all work on genome editing.
The
Chinese Academy of Medical Sciences
Peking Union Medical College (), founded in 1906, is a selective public medical college based in Dongcheng, Beijing, China. It is a Chinese Ministry of Education Double First Class University Plan university. The school is tied to the Peking Un ...
responded to the controversy in the journal
''Lancet'', condemning He for violating ethical guidelines documented by the government and emphasising that germline engineering should not be performed for reproductive purposes. The academy ensured they would "issue further operational, technical and ethical guidelines as soon as possible" to impose tighter regulation on human embryo editing.
Ethical considerations
Editing embryos, germ cells and the generation of designer babies is the subject of ethical debate, as a result of the implications in modifying genomic information in a heritable manner. This includes arguments over unbalanced gender selection and gamete selection.
Despite regulations set by individual countries' governing bodies, the absence of a standardized regulatory framework leads to frequent discourse in discussion of germline engineering among scientists, ethicists and the general public.
Arthur Caplan
Arthur L. Caplan (born 1950) is the Drs. William F. and Virginia Connolly Mitty Professor of Bioethics at New York University Grossman School of Medicine and the founding director of the Division of Medical Ethics.
Caplan has made many contribut ...
, the head of the Division of Bioethics at
New York University
New York University (NYU) is a private research university in New York City. Chartered in 1831 by the New York State Legislature, NYU was founded by a group of New Yorkers led by then-Secretary of the Treasury Albert Gallatin.
In 1832, the ...
suggests that establishing an international group to set guidelines for the topic would greatly benefit global discussion and proposes instating "religious and ethics and legal leaders" to impose well-informed regulations.
In many countries, editing embryos and germline modification for reproductive use is illegal.
As of 2017, the U.S. restricts the use of germline modification and the procedure is under heavy regulation by the FDA and NIH.
The American
National Academy of Sciences
The National Academy of Sciences (NAS) is a United States nonprofit, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the Nati ...
and
National Academy of Medicine
The National Academy of Medicine (NAM), formerly called the Institute of Medicine (IoM) until 2015, is an American nonprofit, non-governmental organization. The National Academy of Medicine is a part of the National Academies of Sciences, En ...
indicated they would provide qualified support for human germline editing "for serious conditions under stringent oversight", should safety and efficiency issues be addressed. In 2019, World Health Organization called human germline genome editing as "irresponsible".
Since genetic modification poses risk to any
organism
In biology, an organism () is any living system that functions as an individual entity. All organisms are composed of cells (cell theory). Organisms are classified by taxonomy into groups such as multicellular animals, plants, and ...
, researchers and medical professionals must give the prospect of germline engineering careful consideration. The main ethical concern 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.
Some bioethicists, including
Ronald Green of
Dartmouth College
Dartmouth College (; ) is a private research university in Hanover, New Hampshire. Established in 1769 by Eleazar Wheelock, it is one of the nine colonial colleges chartered before the American Revolution. Although founded to educate Native A ...
, raise concern that this could result in the accidental introduction of new diseases in future.
When considering support for research into germline engineering, ethicists have often suggested that it can be considered unethical not to consider a technology that could improve the lives of children who would be born with
congenital disorders
A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...
. Geneticist George Church claims that he does not expect germline engineering to increase societal disadvantage, and recommends lowering costs and improving education surrounding the topic to dispel these views.
He emphasizes that allowing germline engineering in children who would otherwise be born with congenital defects could save around 5% of babies from living with potentially avoidable diseases. Jackie Leach Scully, professor of social and
bioethics
Bioethics is both a field of study and professional practice, interested in ethical issues related to health (primarily focused on the human, but also increasingly includes animal ethics), including those emerging from advances in biology, med ...
at
Newcastle University
Newcastle University (legally the University of Newcastle upon Tyne) is a UK public university, public research university based in Newcastle upon Tyne, North East England. It has overseas campuses in Singapore and Malaysia. The university is ...
, acknowledges that the prospect of designer babies could leave those living with diseases and unable to afford the technology feeling marginalized and without medical support.
However, Professor Leach Scully also suggests that germline editing provides the option for parents "to try and secure what they think is the best start in life" and does not believe it should be ruled out. Similarly,
Nick Bostrom
Nick Bostrom ( ; sv, Niklas Boström ; born 10 March 1973) is a Swedish-born philosopher at the University of Oxford known for his work on existential risk, the anthropic principle, human enhancement ethics, superintelligence risks, and the rev ...
, an
Oxford
Oxford () is a city in England. It is the county town and only city of Oxfordshire. In 2020, its population was estimated at 151,584. It is north-west of London, south-east of Birmingham and north-east of Bristol. The city is home to the ...
philosopher
A philosopher is a person who practices or investigates philosophy. The term ''philosopher'' comes from the grc, φιλόσοφος, , translit=philosophos, meaning 'lover of wisdom'. The coining of the term has been attributed to the Greek th ...
known for his work on the risks of
artificial intelligence
Artificial intelligence (AI) is intelligence—perceiving, synthesizing, and inferring information—demonstrated by machines, as opposed to intelligence displayed by animals and humans. Example tasks in which this is done include speech re ...
, proposed that "super-enhanced" individuals could "change the world through their creativity and discoveries, and through innovations that everyone else would use", highlighting not only a personal but societal benefit.
Many bioethicists emphasize that germline engineering is usually considered in the best interest of a child, therefore associated should be supported.
Dr James Hughes, a bioethicist at
Trinity College, Connecticut
Trinity College is a Private university, private Liberal arts colleges in the United States, liberal arts college in Hartford, Connecticut. Founded as Washington College in 1823, it is the second-oldest college in the state of Connecticut.
Coed ...
, suggests that the decision may not differ greatly from others made by parents which are well accepted – choosing with whom to have a child and using contraception to denote when a child is conceived.
Julian Savulescu
Julian Savulescu (born 22 December 1963) is an Australian philosopher and bioethicist of Romanian origins. He is Uehiro Chair in Practical Ethics at the University of Oxford, Fellow of St Cross College, Oxford, director of the Oxford Uehiro Cen ...
, a bioethicist and philosopher at Oxford University believes parents "should allow selection for non‐disease genes even if this maintains or increases social inequality", coining the term
''procreative beneficence'' to describe the idea that the children "expected to have the best life" should be selected.
The
Nuffield Council on Bioethics
The Nuffield Council on Bioethics is a UK-based independent charitable body, which examines and reports on bioethical issues raised by new advances in biological and medical research. Established in 1991, the Council is funded by the Nuffield F ...
said in 2017 that there was "no reason to rule out" changing the DNA of a human embryo if performed in the child's interest, but stressed that this was only provided that it did not contribute to societal inequality.
Furthermore, Nuffield Council in 2018 detailed applications, which would preserve equality and benefit humanity, such as elimination of hereditary disorders and adjusting to warmer climate.
Philosopher and Director of Bioethics at non-profit
Invincible Wellbeing
Invincible may refer to:
Film and television
* ''Invincible'' (2001 drama film), a drama by Werner Herzog about Jewish cabaret during the rise of Nazism
* ''Invincible'' (2001 TV film), a fantasy / martial arts TV movie starring Billy Zane
...
David Pearce argues that "the question
f designer babiescomes down to an analysis of risk-reward ratios - and our basic ethical values, themselves shaped by our evolutionary past." According to Pearce,"it's worth recalling that each act of old-fashioned sexual reproduction is itself an untested genetic experiment", often compromising a child's wellbeing and pro-social capacities even if the child grows in a healthy environment. Pearce thinks that as technology matures, more people may find it unacceptable to rely on "genetic roulette of natural selection".
Conversely, several concerns have been raised regarding the possibility of generating designer babies, especially concerning the inefficiencies currently presented by the technologies. Bioethicist Ronald Green stated that although the technology was "unavoidably in our future", he foresaw "serious errors and health problems as unknown genetic side effects in 'edited' children" arise.
Furthermore, Green warned against the possibility that "the well-to-do" could more easily access the technologies "..that make them even better off". This concern regarding germline editing exacerbating a societal and financial divide is shared amongst other researches, with the chair of the Nuffield Bioethics Council Professor Karen Yeung stressing that if funding of the procedures "were to exacerbate social injustice, in our view that would not be an ethical approach".
Social and religious worries also arise over the possibility of editing human embryos. In a survey conducted by the
Pew Research Centre
The Pew Research Center is a nonpartisan American think tank (referring to itself as a "fact tank") based in Washington, D.C.
It provides information on social issues, public opinion, and demographic trends shaping the United States and the wor ...
, it was found that only a third of the Americans surveyed who identified as strongly
Christian
Christians () are people who follow or adhere to Christianity, a monotheistic Abrahamic religion based on the life and teachings of Jesus Christ. The words ''Christ'' and ''Christian'' derive from the Koine Greek title ''Christós'' (Χρι ...
approved of germline editing.
Catholic leaders are in the middle ground. This stance is because, according to Catholicism, a baby is a gift from God, and Catholics believe that people are created to be perfect in God's eyes. Thus, altering the genetic makeup of an infant is unnatural. In 1984, Pope John Paul II addressed that genetic manipulation in aiming to heal diseases is acceptable in the Church. He stated that it "will be considered in principle as desirable provided that it tends to the real promotion of the personal well-being of man, without harming his integrity or worsening his life conditions".
However, it is unacceptable if designer babies are used to create a super/superior race including cloning humans. The Catholic Church rejects human cloning even if its purpose is to produce organs for therapeutic usage. The Vatican has stated that "The fundamental values connected with the techniques of artificial human procreation are two: the life of the human being called into existence and the special nature of the transmission of human life in marriage". According to them, it violates the dignity of the individual and is morally illicit.
A survey conducted by the Mayo Clinic in the Midwestern United States in 2017 saw that most of the participants agreed against the creation of designer babies with some noting its eugenic undertones.
The participants also felt that gene editing may have unintended consequences that it may be manifested later in life for those that undergo gene editing.
Some that took the survey worried that gene editing may lead to a decrease in the genetic diversity of the population in societies.
The survey also noted how the participants were worried about the potential socioeconomic effects designer babies may exacerbate.
The authors of the survey noted that the results of the survey showed that there is a greater need for interaction between the public and the scientific community concerning the possible implications and the recommended regulation of gene editing as it was unclear to them how much those that participated knew about gene editing and its effects prior to taking the survey.
In Islam, the positive attitude towards genetic engineering is based on the general principle that Islam aims at facilitating human life. However, the negative view comes from the process used to create a Designer baby. Oftentimes, it involves the destruction of some embryos. Muslims believe that "embryos already has a soul" at conception. Thus, the destruction of embryos is against the teaching of the Qur'an, Hadith, and Shari'ah law, that teaches our responsibility to protect human life. To clarify, the procedure would be viewed as "acting like God/Allah". With the idea, that parents could choose the gender of their child, Islam believes that humans have no decision to choose the gender, and that "gender selection is only up to God".
In 2020, There has been discussion about American studies that used embryos without embryonic implantation with the CRISPR/Cas9 technique that had been modified with HDR (homology-directed repair) and the conclusions from the results were that gene editing technologies are not mature enough currently for real world use and that there is a need for more studies that generate safe results over a longer period of time.
An article in the journal, ''Bioscience Reports,'' discussed how health in terms of genetics is not straightforward and thus there should be extensive deliberation for operations involving gene editing when the technology gets mature enough for real world use where all of the potential effects are known on a case-by-case basis to prevent undesired effects on the subject or patient being operated on.
Social aspects also raise concern, as highlighted by Josephine Quintavelle, director of ''Comment on Reproductive Ethics'' at
Queen Mary University of London
, mottoeng = With united powers
, established = 1785 – The London Hospital Medical College1843 – St Bartholomew's Hospital Medical College1882 – Westfield College1887 – East London College/Queen Mary College
, type = Public researc ...
, who states that selecting children's traits is "turning parenthood into an unhealthy model of self-gratification rather than a relationship".
One major worry among scientists, including
Marcy Darnovsky at the
Center for Genetics and Society in
California
California is a U.S. state, state in the Western United States, located along the West Coast of the United States, Pacific Coast. With nearly 39.2million residents across a total area of approximately , it is the List of states and territori ...
, is that permitting germline engineering for correction of disease phenotypes is likely to lead to its use for cosmetic purposes and enhancement.
Meanwhile,
Henry Greely
Henry T. "Hank" Greely is an American lawyer, a leading authority on the ethical, legal, and social implications of new biomedical technologies, particularly those related to genetics, assisted reproduction, neuroscience and stem cell research.
G ...
, a bioethicist at
Stanford University
Stanford University, officially Leland Stanford Junior University, is a private research university in Stanford, California. The campus occupies , among the largest in the United States, and enrolls over 17,000 students. Stanford is consider ...
in California, states that "almost everything you can accomplish by gene editing, you can accomplish by embryo selection", suggesting the risks undertaken by germline engineering may not be necessary.
Alongside this, Greely emphasizes that the beliefs that genetic engineering will lead to enhancement are unfounded, and that claims that we will enhance intelligence and personality are far off – "we just don't know enough and are unlikely to for a long time – or maybe for ever".
See also
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Biohappiness Biohappiness, or bio-happiness, is the elevation of wellbeing in humans through biological methods, including germline engineering through screening embryos with genes associated with a high level of happiness, or the use of drugs intended to raise ...
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Directed evolution (transhumanism)
The term directed evolution is used within the transhumanist community to refer to the idea of applying the principles of directed evolution and experimental evolution to the control of human evolution. In this sense, it is distinct from the use ...
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Epidemiology of genetic disorder
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Eugenics
Eugenics ( ; ) is a fringe set of beliefs and practices that aim to improve the genetic quality of a human population. Historically, eugenicists have attempted to alter human gene pools by excluding people and groups judged to be inferior or ...
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Eugenics in the United States
Eugenics, the set of beliefs and practices which aims at improving the genetic quality of the human population, played a significant role in the history and culture of the United States from the late 19th century into the mid-20th century. T ...
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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 ...
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Human enhancement
Human enhancement (HE) can be described as the natural, artificial, or technological alteration of the human body in order to enhance physical or mental capabilities.
Technologies
Existing technologies
Three forms of human enhancement curre ...
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Human genetic engineering
Human genetic enhancement or human genetic engineering refers to human enhancement by means of a genetic modification. This could be done in order to cure diseases (gene therapy), prevent the possibility of getting a particular disease (similarly ...
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Human germline engineering
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Liberal eugenics
New eugenics, also known as liberal eugenics (a term coined by bioethicist Nicholas Agar), advocates enhancing human characteristics and capacities through the use of reproductive technology and human genetic engineering. Those who advocate new eu ...
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Lulu and Nana
The He Jiankui affair is a scientific and Bioethics, bioethical controversy concerning the use of genome editing following its first use on humans by Chinese scientist He Jiankui, who edited the genomes of human embryos in 2018. He became widel ...
(Gene edited babies in China 2018)
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Moral enhancement
Moral enhancement (abbreviated ME), also called moral bioenhancement (abbreviated MBE), is the use of biomedical technology to morally improve individuals. MBE is a growing topic in neuroethics, a field developing the ethics of neuroscience as well ...
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Reprogenetics
Assisted reproductive technology (ART) includes medical procedures used primarily to address infertility. This subject involves procedures such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), cryopreservation of gametes ...
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Transhumanism
Transhumanism is a philosophical and intellectual movement which advocates the enhancement of the human condition by developing and making widely available sophisticated technologies that can greatly enhance longevity and cognition.
Transhuma ...
References
Further reading
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* A non-fiction account of Strongin's pioneering use of IVF and PGD to have a healthy child whose cord blood could save the life of her son Henry
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1989 introductions
2018 introductions
Bioethics
Emerging technologies
Ethically disputed medical practices
Fertility medicine
Genetic engineering
Genome editing
Human reproduction
Transhumanism