Human Genetic Engineering
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Human genetic enhancement or human genetic engineering refers to
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 ...
by means of a
genetic modification Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of technologies used to change the genetic makeup of cells, including t ...
. This could be done in order to cure diseases (
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 ...
), prevent the possibility of getting a 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 ...
(similarly to vaccines), to improve athlete performance in sporting events (
gene doping Gene doping is the hypothetical non-therapeutic use of gene therapy by athletes in order to improve their performance in those sporting events which prohibit such applications of genetic modification technology, and for reasons other than the treat ...
), or to change physical appearance, metabolism, and even improve physical capabilities and mental faculties such as memory and intelligence. These genetic enhancements may or may not be done in such a way that the change is heritable (which has raised concerns within the scientific community).


Gene therapy

Genetic modification in order to cure genetic diseases is referred to as
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 ...
. Many such gene therapies are available, made it through all phases of clinical research and are approved by the FDA. Between 1989 and December 2018, over 2,900 clinical trials were conducted, with more than half of them in phase I.s , Spark Therapeutics' Luxturna ( RPE65 mutation-induced blindness) and Novartis' Kymriah (
Chimeric antigen receptor T cell In biology, chimeric antigen receptors (CARs)—also known as chimeric immunoreceptors, chimeric T cell receptors or artificial T cell receptors—are receptor proteins that have been engineered to give T cells the new ability to target a specifi ...
therapy) are the FDA's first approved gene therapies to enter the market. Since that time, drugs such as Novartis'
Zolgensma Onasemnogene abeparvovec, sold under the brand name Zolgensma, is a gene therapy medication used to treat spinal muscular atrophy (SMA). It is used as a one-time infusion into a vein. Onasemnogene abeparvovec works by providing a new copy of ...
and Alnylam's
Patisiran Patisiran, sold under the brand name Onpattro, is a medication used for the treatment of polyneuropathy in people with hereditary transthyretin-mediated amyloidosis, a fatal rare disease that is estimated to affect 50,000 people worldwide. It is ...
have also received FDA approval, in addition to other companies' gene therapy drugs. Most of these approaches utilize
adeno-associated virus Adeno-associated viruses (AAV) are small viruses that infect humans and some other primate species. They belong to the genus ''Dependoparvovirus'', which in turn belongs to the family ''Parvoviridae''. They are small (approximately 26 nm in di ...
es (AAVs) and
lentivirus ''Lentivirus'' is a genus of retroviruses that cause chronic and deadly diseases characterized by long incubation periods, in humans and other mammalian species. The genus includes the human immunodeficiency virus (HIV), which causes AIDS. Lent ...
es for performing gene insertions, ''
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 ...
'' and ''
ex vivo ''Ex vivo'' (Latin: "out of the living") literally means that which takes place outside an organism. In science, ''ex vivo'' refers to experimentation or measurements done in or on tissue from an organism in an external environment with minimal ...
'', respectively. ASO /
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 ...
approaches such as those conducted by Alnylam and
Ionis Pharmaceuticals Ionis Pharmaceuticals, Inc. is a biotechnology company based in Carlsbad, California, that specializes in discovering and developing RNA-targeted therapeutics. The company has 3 commercially approved medicines: Spinraza (Nusinersen), Tegsedi ( I ...
require non-viral delivery systems, and utilize alternative mechanisms for trafficking to liver cells by way of GalNAc transporters.


Disease prevention

Some people are
immunocompromised Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
and their bodies are hence much less capable of fending off and defeating diseases (i.e. influenza, ...). In some cases this is due to genetic flaws or even
genetic 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 ...
s such as SCID. Some gene therapies have already been developed or are being developed to correct these genetic flaws/diseases, hereby making these people less susceptible to catching additional diseases (i.e. influenza, ...). In November 2018,
Lulu and Nana The He Jiankui affair is a scientific and 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 widely known on ...
were created. By using clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9, a gene editing technique, they disabled a gene called CCR5 in the embryos, aiming to close the protein doorway that allows HIV to enter a cell and make the subjects immune to the HIV virus.


Gene doping

Athletes might adopt gene therapy technologies to improve their performance.
Gene doping Gene doping is the hypothetical non-therapeutic use of gene therapy by athletes in order to improve their performance in those sporting events which prohibit such applications of genetic modification technology, and for reasons other than the treat ...
is not known to occur, but multiple gene therapies may have such effects. Kayser et al. argue that gene doping could level the playing field if all athletes receive equal access. Critics claim that any therapeutic intervention for non-therapeutic/enhancement purposes compromises the ethical foundations of medicine and sports.


Other uses

Other hypothetical gene therapies could include changes to physical appearance, metabolism, mental faculties such as memory and intelligence, and well-being (by increasing resistance to depression or relieving
chronic pain Chronic pain is classified as pain that lasts longer than three to six months. In medicine, the distinction between Acute (medicine), acute and Chronic condition, chronic pain is sometimes determined by the amount of time since onset. Two commonly ...
, for example).


Physical appearance

Some congenital disorders (such as those affecting the muscoskeletal system) may affect physical appearance, and in some cases may also cause physical discomfort. Modifying the genes causing these congenital diseases (on those diagnosed to have mutations of the gene known to cause these diseases) may prevent this. Also changes in the mystatin gene may alter appearance.


Behavior

Behavior Behavior (American English) or behaviour (British English) is the range of actions and mannerisms made by individuals, organisms, systems or artificial entities in some environment. These systems can include other systems or organisms as wel ...
may also be modified by genetic intervention. Some people may be aggressive, selfish, and may not be able to function well in society. There is currently research ongoing on genes that are or may be (in part) responsible for selfishness (e.g. ruthlessness gene), aggression (e.g.
warrior gene Monoamine oxidase A, also known as MAO-A, is an enzyme that in humans is encoded by the ''MAOA'' gene. This gene is one of two neighboring gene family members that encode mitochondrial enzymes which catalyze the oxidative deamination of amines, ...
), altruism (e.g.
OXTR The oxytocin receptor, also known as OXTR, is a protein which functions as receptor for the hormone and neurotransmitter oxytocin. In humans, the oxytocin receptor is encoded by the ''OXTR'' gene which has been localized to human chromosome 3p ...
, CD38,
COMT Catechol-''O''-methyltransferase (COMT; ) is one of several enzymes that degrade catecholamines (neurotransmitters such as dopamine, epinephrine, and norepinephrine), catecholestrogens, and various drugs and substances having a catechol structu ...
,
DRD4 The dopamine receptor D4 is a dopamine D2-like G protein-coupled receptor encoded by the gene on chromosome 11 at 11p15.5. The structure of DRD4 was recently reported in complex with the antipsychotic drug nemonapride. As with other dopamine ...
,
DRD5 Dopamine receptor D5, also known as D1BR, is a protein that in humans is encoded by the ''DRD5'' gene. It belongs to the D1-like receptor family along with the D1 receptor subtype. Function D5 receptor is a subtype of the dopamine receptor ...
,
IGF2 Insulin-like growth factor 2 (IGF-2) is one of three protein hormones that share structural similarity to insulin. The MeSH definition reads: "A well-characterized neutral peptide believed to be secreted by the liver and to circulate in the bloo ...
,
GABRB2 The GABAA beta-2 subunit is a protein that in humans is encoded by the GABRB2 gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or '' ...
) There is some research going on on the hypothetical treatment of psychiatric disorders by means of gene therapy. It is assumed that, with gene-transfer techniques, it is possible (in experimental settings using animal models) to alter CNS gene expression and thereby the intrinsic generation of molecules involved in neural plasticity and neural regeneration, and thereby modifying ultimately behaviour. In recent years, it was possible to modify ethanol intake in animal models. Specifically, this was done by targeting the expression of the aldehyde dehydrogenase gene (ALDH2), lead to a significantly altered alcohol-drinking behaviour. Reduction of p11, a serotonin receptor binding protein, in the nucleus accumbens led to depression-like behaviour in rodents, while restoration of the p11 gene expression in this anatomical area reversed this behaviour. Recently, it was also shown that the gene transfer of CBP (CREB (c-AMP response element binding protein) binding protein) improves cognitive deficits in an animal model of Alzheimer's dementia via increasing the expression of BDNF (brain-derived neurotrophic factor). The same authors were also able to show in this study that accumulation of amyloid-β (Aβ) interfered with CREB activity which is physiologically involved in memory formation. In another study, it was shown that Aβ deposition and plaque formation can be reduced by sustained expression of the neprilysin (an endopeptidase) gene which also led to improvements on the behavioural (i.e. cognitive) level. Similarly, the intracerebral gene transfer of ECE (endothelin-converting enzyme) via a virus vector stereotactically injected in the right anterior cortex and hippocampus, has also shown to reduce Aβ deposits in a transgenic mouse model of Alzeimer's dementia. There is also research going on on genoeconomics, a
protoscience __NOTOC__ In the philosophy of science, there are several definitions of protoscience. Its simplest meaning (most closely reflecting its roots of '' proto-'' + ''science'') involves the earliest eras of the history of science, when the scientific m ...
that is based on the idea that a person's
financial Finance is the study and discipline of money, currency and capital assets. It is related to, but not synonymous with economics, the study of production, distribution, and consumption of money, assets, goods and services (the discipline of fina ...
behavior could be traced to their DNA and that
genes 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 ...
are related to
economic behavior Behavioral economics studies the effects of psychological, cognitive, emotional, cultural and social factors on the decisions of individuals or institutions, such as how those decisions vary from those implied by classical economic theory ...
. , the results have been inconclusive. Some minor correlations have been identified.


Databases about potential modifications

George Church has compiled a list of potential genetic modifications based on scientific studies for possibly advantageous traits such as less need for sleep, cognition-related changes that protect against Alzheimer's disease, disease resistances, higher lean muscle mass and enhanced
learning Learning is the process of acquiring new understanding, knowledge, behaviors, skills, value (personal and cultural), values, attitudes, and preferences. The ability to learn is possessed by humans, animals, and some machine learning, machines ...
abilities along with some of the associated studies and potential negative effects.


See also

*
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 ...
*
Crossbreed A crossbreed is an organism with purebred parents of two different breeds, varieties, or populations. ''Crossbreeding'', sometimes called "designer crossbreeding", is the process of breeding such an organism, While crossbreeding is used to main ...
ing *
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 ...
*
Designer baby A designer baby is a baby whose genetics, genetic makeup has been selected or altered, often to not include a particular gene or to remove genes associated with disease. This process usually involves analysing a wide range of human embryos to ide ...
*
Epigenetics In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
*
Genetic screening Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...
: allows detecting personal genetic weaknesses to be addressed * Genetic factors of addiction * Procreative beneficence *
New 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 e ...
*
Life extension Life extension is the concept of extending the human life expectancy, lifespan, either modestly through improvements in medicine or dramatically by increasing the maximum lifespan beyond its generally-settled oldest people, limit of 125 years. S ...


References

{{Human genetics * Emerging technologies Biological engineering Body modification Biotechnology Molecular biology Engineering disciplines