From Wikipedia, the free encyclopedia
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 to vaccines), to improve athlete performance in sporting events (gene doping),
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.
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. As of 2017, Spark Therapeutics' Luxturna (RPE65 mutation-induced blindness) and Novartis' Kymriah (Chimeric antigen receptor T cell therapy) are the FDA's first approved gene therapies to enter the market. Since that time, drugs such as Novartis' Zolgensma and Alnylam's Patisiran have also received FDA approval, in addition to other companies' gene therapy drugs. Most of these approaches utilize adeno-associated viruses (AAVs) and lentiviruses for performing gene insertions, in vivo and ex vivo, respectively. ASO / siRNA approaches such as those conducted by Alnylam and Ionis Pharmaceuticals 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
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 diseases 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 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 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, 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 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), altruism (e.g. OXTR, CD38, COMT, DRD4, DRD5, IGF2, GABRB2)
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 that is based on the idea that a person's financial behavior could be traced to their DNA and that genes are related to economic behavior. As of 2015, 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 abilities along with some of the associated studies and potential negative effects.
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 to vaccines), to improve athlete performance in sporting events (gene doping),
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.
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. As of 2017, Spark Therapeutics' Luxturna (RPE65 mutation-induced blindness) and Novartis' Kymriah (Chimeric antigen receptor T cell therapy) are the FDA's first approved gene therapies to enter the market. Since that time, drugs such as Novartis' Zolgensma and Alnylam's Patisiran have also received FDA approval, in addition to other companies' gene therapy drugs. Most of these approaches utilize adeno-associated viruses (AAVs) and lentiviruses for performing gene insertions, in vivo and ex vivo, respectively. ASO / siRNA approaches such as those conducted by Alnylam and Ionis Pharmaceuticals 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
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 diseases 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 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 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, 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 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), altruism (e.g. OXTR, CD38, COMT, DRD4, DRD5, IGF2, GABRB2)
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 that is based on the idea that a person's financial behavior could be traced to their DNA and that genes are related to economic behavior. As of 2015, 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 abilities along with some of the associated studies and potential negative effects.
