Marker assisted selection or marker aided selection (MAS) is an indirect selection process where a trait of interest is selected based on a marker (morphological, biochemical or DNA/RNA
variation) linked to a trait of interest (e.g. productivity, disease
resistance, abiotic stress tolerance, and quality), rather than on the
trait itself. This process has been extensively researched and proposed for plant- and animal- breeding.
For example, using MAS to select individuals with disease resistance involves identifying a marker allele
that is linked with disease resistance rather than the level of disease
resistance. The assumption is that the marker associates at high
frequency with the gene or quantitative trait locus
(QTL) of interest, due to genetic linkage (close proximity, on the
chromosome, of the marker locus and the disease resistance-determining
locus). MAS can be useful to select for traits that are difficult or
expensive to measure, exhibit low heritability
and/or are expressed late in development. At certain points in the
breeding process the specimens are examined to ensure that they express
the desired trait.
Marker types
The majority of MAS work in the present era uses DNA-based markers. However, the first markers that allowed indirect selection of a trait
of interest were morphological markers. In 1923, Karl Sax first
reported association of a simply inherited genetic marker
with a quantitative trait in plants when he observed segregation of
seed size associated with segregation for a seed coat color marker in
beans (Phaseolus vulgaris L.). In 1935, J. Rasmusson demonstrated linkage of flowering time (a quantitative trait) in peas with a simply inherited gene for flower color.
Markers may be:
Morphological — These were the first markers loci
available that have an obvious impact on the morphology of plants.
These markers are often detectable by eye, by simple visual inspection.
Examples of this type of marker include the presence or absence of an awn, leaf sheath coloration, height, grain color, aroma of rice etc. In well-characterized crops like maize, tomato, pea, barley or wheat, tens or hundreds of genes that determine morphological traits have been mapped to specific chromosome locations.
Biochemical — A protein that can be extracted and observed; for example, isozymes and storage proteins.
Cytological — Cytological markers are chromosomal features that can be identified through microscopy. These generally take the form of chromosome bands, regions of chromatin that become impregnated with specific dyes used in cytology. The presence or absence of a chromosome band
can be correlated with a particular trait, indicating that the locus
responsible for the trait is located within or near (tightly linked) to
the banded region. Morphological and cytological markers formed the
backbone of early genetic studies in crops such as wheat and maize.
The
following terms are generally less relevant to discussions of MAS in
plant and animal breeding, but are highly relevant in molecular biology
research:
Positive selectable markers are selectable markers that confer selective advantage to the host organism. An example would be antibiotic resistance, which allows the host organism to survive antibiotic selection.
Negative selectable markers are selectable markers that eliminate or inhibit growth of the host organism upon selection. An example would be thymidine kinase, which makes the host sensitive to ganciclovir selection.
A distinction can be made between selectable markers (which eliminate
certain genotypes from the population) and screenable markers (which
cause certain genotypes to be readily identifiable, at which point the
experimenter must "score" or evaluate the population and act to retain
the preferred genotypes). Most MAS uses screenable markers rather than
selectable markers.
Gene vs marker
The
gene of interest directly causes production of protein(s) or RNA that
produce a desired trait or phenotype, whereas markers (a DNA sequence
or the morphological or biochemical markers produced due to that DNA)
are genetically linked to the gene of interest. The gene of interest
and the marker tend to move together during segregation of gametes due
to their proximity on the same chromosome and concomitant reduction in recombination
(chromosome crossover events) between the marker and gene of interest.
For some traits, the gene of interest has been discovered and the
presence of desirable alleles can be directly assayed with a high level
of confidence. However, if the gene of interest is not known, markers
linked to the gene of interest can still be used to select for
individuals with desirable alleles of the gene of interest. When
markers are used there may be some inaccurate results due to inaccurate
tests for the marker. There also can be false positive results when
markers are used, due to recombination between the marker of interest
and gene (or QTL). A perfect marker would elicit no false positive
results. The term 'perfect marker' is sometimes used when tests are
performed to detect a SNP or other DNA polymorphism in the gene of
interest, if that SNP or other polymorphism is the direct cause of the
trait of interest. The term 'marker' is still appropriate to use when
directly assaying the gene of interest, because the test of genotype is
an indirect test of the trait or phenotype of interest.
Important properties of ideal markers for MAS
An ideal marker:
Has easy recognition of phenotypes - ideally all possible phenotypes (homo- and heterozygotes) from all possible alleles
Demonstrates measurable differences in expression between trait
types or gene of interest alleles, early in the development of the
organism
Testing for the marker does not have variable success depending on
the allele at the marker locus or the allele at the target locus (the
gene of interest that determines the trait of interest).
Low or null interaction among the markers allowing the use of many at the same time in a segregating population
Morphological markers are associated with several general deficits that reduce their usefulness including:
the delay of marker expression until late into the development of the organism
allowing dominance to mask the underlying genetics
pleiotropy, which does not allow easy and parsimonious inferences to be drawn from one gene to one trait
confounding effects of genes unrelated to the gene or trait of interest but which also affect the morphological marker (epistasis)
frequent confounding effects of environmental factors which affect the morphological characteristics of the organism
To avoid problems specific to morphological markers, DNA-based markers have been developed. They are highly polymorphic,
exhibit simple inheritance (often codominant), are abundant throughout
the genome, are easy and fast to detect, exhibit minimum pleiotropic
effects, and detection is not dependent on the developmental stage of
the organism. Numerous markers have been mapped to different chromosomes
in several crops including rice, wheat, maize, soybean and several
others, and in livestock such as cattle, pigs and chickens. Those
markers have been used in diversity analysis, parentage detection, DNA
fingerprinting, and prediction of hybrid performance. Molecular markers
are useful in indirect selection processes, enabling manual selection of
individuals for further propagation.
Selection for major genes linked to markers
'Major
genes' that are responsible for economically important characteristics
are frequent in the plant kingdom. Such characteristics include disease
resistance, male sterility, self-incompatibility, and others related to shape, color, and
architecture of whole plants and are often of mono- or oligogenic in
nature. The marker loci that are tightly linked to major genes can be
used for selection and are sometimes more efficient than direct
selection for the target gene. Such advantages in efficiency may be due
for example, to higher expression of the marker mRNA in such cases that
the marker is itself a gene. Alternatively, in such cases that the
target gene of interest differs between two alleles by a
difficult-to-detect single nucleotide polymorphism, an external marker (be it another gene or a polymorphism that is easier to detect, such as a short tandem repeat) may present as the most realistic option.
Situations that are favorable for molecular marker selection
There are several indications for the use of molecular markers in the selection of a genetic trait.
Situations such as:
The selected character is expressed late in plant development,
like fruit and flower features or adult characters with a juvenile
period (so that it is not necessary to wait for the organism to become
fully developed before arrangements can be made for propagation)
The expression of the target gene is recessive (so that individuals which are heterozygous positive for the recessive allele can be crossed to produce some homozygous offspring with the desired trait)
There are special conditions for expression of the target gene(s),
as in the case of breeding for disease and pest resistance (where
inoculation with the disease or subjection to pests would otherwise be
required). Sometimes inoculation methods are unreliable and sometimes
field inoculation with the pathogen is not even allowed for safety
reasons. Moreover, sometimes expression is dependent on environmental
conditions.
The phenotype is affected by two or more unlinked genes (epistatis).
For example, selection for multiple genes which provide resistance
against diseases or insect pests for gene pyramiding.
The cost of genotyping
(for example, the molecular marker assays needed here) is decreasing
thus increasing the attractiveness of MAS as the development of the
technology continues. (Additionally, the cost of phenotyping performed by a human is a labor burden, which is higher in a developed country and increasing in a developing country.)
Steps for MAS
Generally the first step is to map the gene or quantitative trait locus
(QTL) of interest first by using different techniques and then using
this information for marker assisted selection. Generally, the markers
to be used should be close to gene of interest (<5 recombination unit
or cM) in order to ensure that only minor fraction of the selected
individuals will be recombinants. Generally, not only a single marker
but rather two markers are used in order to reduce the chances of an
error due to homologous recombination. For example, if two flanking
markers are used at same time with an interval between them of
approximately 20cM, there is higher probability (99%) for recovery of
the target gene.
In plants QTL mapping is generally achieved using bi-parental cross
populations; a cross between two parents which have a contrasting
phenotype for the trait of interest are developed. Commonly used
populations are near isogenic lines (NILs), recombinant inbred lines
(RILs), doubled haploids (DH), back cross and F2.
Linkage between the phenotype and markers which have already been
mapped is tested in these populations in order to determine the position
of the QTL. Such techniques are based on linkage and are therefore
referred to as "linkage mapping".A
Single step MAS and QTL mapping
In contrast to two-step QTL mapping and MAS, a single-step method for breeding typical plant populations has been developed.
In such an approach, in the first few breeding cycles, markers
linked to the trait of interest are identified by QTL mapping and later
the same information is used in the same population. In this approach,
pedigree structure is created from families that are created by crossing
number of parents (in three-way or four way crosses). Both phenotyping
and genotyping is done using molecular markers mapped the possible
location of QTL of interest. This will identify markers and their
favorable alleles. Once these favorable marker alleles are identified,
the frequency of such alleles will be increased and response to marker
assisted selection is estimated. Marker allele(s) with desirable effect
will be further used in next selection cycle or other experiments.
High-throughput genotyping techniques
Recently
high-throughput genotyping techniques are developed which allows marker
aided screening of many genotypes. This will help breeders in shifting
traditional breeding to marker aided selection. One example of such
automation is using DNA isolation robots, capillary electrophoresis and
pipetting robots.
One recent example of capllilary system is Applied Biosystems
3130 Genetic Analyzer. This is the latest generation of 4-capillary
electrophoresis instruments for the low to medium throughput
laboratories.
High-throughput MAS is needed for crop breeding
because current techniques are not cost effective. Arrays have been
developed for rice by Masouleh et al 2009; wheat by Berard et al 2009,
Bernardo et al 2015, and Rasheed et al 2016; legumes by Varshney et al
2016; and various other crops, but all of these have also problems with
customization, cost, flexibility, and equipment costs.
Use of MAS for backcross breeding
A minimum of five or six-backcross
generations are required to transfer a gene of interest from a donor
(may not be adapted) to a recipient (recurrent – adapted cultivar). The
recovery of the recurrent genotype can be accelerated with the use of
molecular markers. If the F1 is heterozygous for the marker locus, individuals with the recurrent parent allele(s) at the marker locus in first or subsequent backcross generations will also carry a chromosome tagged by the marker.
Marker assisted gene pyramiding
Gene pyramiding
has been proposed and applied to enhance resistance to disease and
insects by selecting for two or more than two genes at a time. For
example, in rice such pyramids have been developed against bacterial
blight and blast. The advantage of use of markers in this case allows to
select for QTL-allele-linked markers that have same phenotypic effect.
MAS has also been proved useful for livestock improvement.
A coordinated effort to implement wheat (Durum (Triticum turgidum) and common wheat (Triticum aestivum)) marker assisted selection in the U.S. as well as a resource for marker assisted selection exists at the Wheat CAP (Coordinated Agricultural Project) website.
A crossbreed is an organism with purebred
parents of two different breeds, varieties, or populations. A domestic
animal of unknown ancestry, where the breed status of only one parent or
grandparent is known, may also be called a crossbreed though the term
"mixed breed" is technically more accurate. Outcrossing
is a type of crossbreeding used within a purebred breed to increase the
genetic diversity within the breed, particularly when there is a need
to avoid inbreeding.
In animal breeding, crossbreeds are crosses within a single species, while hybrids are crosses between different species. In plant breeding terminology, the term crossbreed
is uncommon, and no universal term is used to distinguish hybridization
or crossing within a population from those between populations, or even
those between species.
Crossbreeding is the process of breeding such an organism. It can
be beneficially used to maintain health and viability of organisms.
However, irresponsible crossbreeding can also produce organisms of
inferior quality or dilute a purebred gene pool to the point of extinction of a given breed of organism.
Crossbreeds in specific animals
Cats: The many newly developed and recognized breeds of domestic cat are crossbreeds between existing, well-established breeds (sometimes with limited hybridization with some wild species), to either combine selected traits from the foundation stock, or propagate a rare mutation without excessive inbreeding. However, some nascent breeds such as the Aegean cat are developed entirely from a local landrace population. Most experimental cat breeds are crossbreeds.
Cattle: In cattle, there are systems of crossbreeding. In
many crossbreeds, one animal is larger than the other. One is used when
the purebred females are particularly adapted to a specific environment,
and are crossed with purebred bulls from another environment to produce
a generation having traits of both parents.
Sheep: The large number of breeds of sheep, which vary
greatly, creates an opportunity for crossbreeding to be used to tailor
production of lambs to the goal of the individual stockman.
Llamas: Results of crossbreeding classic and woolly breeds
of llama are unpredictable. The resulting offspring displays physical
characteristics of either parent, or a mix of characteristics from both,
periodically producing a fleeced llama.
The results are increasingly unpredictable when both parents are
crossbreeds, with possibility of the offspring displaying
characteristics of a grandparent, not obvious in either parent.
A crossbred dog is a cross between two (sometimes more) known breeds, and is usually distinguished from a mixed-breed dog,
which has ancestry from many sources, some of which may not be known.
Crossbreeds are popular, due to the belief that they have increased vigor
without loss of attractiveness of the dog. Certain planned
crossbreeding between purebred dogs of different breeds are now widely
known as "designer dogs" and can produce puppies worth more than their
purebred parents, due to a high demand.
Horses:
Crossbreeding horses is often done with the intent of ultimately
creating a new breed of horse. One type of modern crossbreeding in
horses created many of the warmblood breeds used in the sport horse disciplines, usually registered in an open stud book by a studbook selection
procedure that evaluates conformation, pedigree and, in some animals, a
training or performance standard. Most warmblood breeds began as a
cross of draft horse breeds on Thoroughbreds,
but have, in some cases, developed over the past century to the point
where they are considered to be a true-breeding population and have a closed stud book. Other types of recognized crossbreeding include that within the American Quarter Horse,
which will register horses with one Thoroughbred parent and one
registered Quarter Horse parent in the "Appendix" registry, and allow
such animals full breed registration status as Quarter Horses if they
meet a certain performance standard. Another well-known crossbred
horse is the Anglo-Arabian, which may be produced by a purebred Arabian horse
crossed on a Thoroughbred, or by various crosses of Anglo-Arabians with
other Anglo-Arabians, as long as the ensuing animal never has more than
75% or less than 25% of each breed represented in its pedigree.
A hybrid
animal is one with parentage of two separate species, differentiating
it from crossbred animals, which have parentage of the same species.
Hybrids are usually, but not always, sterile.
One of the most ancient types of hybrid animal is the mule, a cross between a female horse and a male donkey. The liger is a hybrid cross between a male lion and female tiger. The yattle is a cross between a cow and a yak. Other crosses include the tigon (between a male tiger and female lion) and yakalo (between a yak and an American bison). The Incas recognized that hybrids of Lama glama (llama) and Vicugna pacos (alpaca) resulted in a hybrid with none of the advantages of either parent.
At one time it was thought that dogs and wolves were separate species, and the crosses between dogs and wolves were called wolf hybrids. Today wolves and dogs are both recognized as Canis lupus, but the old term "wolf hybrid" is still used.
A mixed-breed animal is defined as having undocumented or unknown parentage, while a crossbreed generally has known, usually purebred parents of two distinct breeds or varieties. A dog of unknown parentage is often called a mixed-breed dog, "mutt" or "mongrel." A cat of unknown parentage is often referred to as a domestic short-haired or domestic long-haired cat generically, and in some dialects is often called a "moggie". A horse of unknown bloodlines is called a grade horse.
A designer crossbreed or designer breed is a crossbred animal with purebred parents, usually registered with a breed registry, but from two different breeds. These animals are the result of a deliberate decision to create a specific crossbred animal. Less often, the animal may have more than two pure breeds in its ancestry, but unlike a mutt or a mongrel, its entire pedigree is known to descend from specific known animals. While the term is best known when applied to certain dog crossbreeds, other animals such as cattle, horses, birds and cats may also be bred in this fashion. Some crossbred breeders
start a freestanding breed registry to record designer crossbreds, other
crossbreds may be included in an "appendix" to an existing purebred
registry. either form of registration may be the first step in
recording and tracking pedigrees in order to develop a new breed.
The purpose of creating designer crossbreds is usually one or more of the following reasons:
to breed animals with heterosis, commonly known as "hybrid vigor",
to create animals with more predictable characteristics than mixed breed or mongrel breeding,
to avoid certain undesirable recessive traits that lead to genetic diseases that plague many purebred animals,
to develop an animal that combines what are viewed as the best traits of two or more breeds,
as the preliminary steps toward developing a new animal breed.
Breeders of designer crossbreds borrow the technical language from hybrid plant breeding: A first generation, 50–50 crossbred is an F1 cross. Subsequent generations may see a purebred animal crossed back on a crossbred, creating a 75/25 cross, or a BC1 or F1b "backcross." The breeding of two crossbreeds of the same combination of breeds,
creating an F2 cross, an animal that is still a 50–50 cross, but it is
the second filial generation of the combination. An F2 cross bred to an F2 cross creates an F3 cross. Similarly, an F2
animal bred to an F1 animal creates an F2b backcross. F3 crosses and
greater are called "multi-generational" crosses. In dog breeding, three generations of reliable documented breeding can be considered a "breed" rather than a crossbreed.
There are disadvantages to creating designer crossbreeds, notably
the potential that the cross will be of inferior quality or that it
will not produce as consistent a result as would breeding purebred
animals. For example, the Poodle
is a frequent breed used in creation of designer crossbreeds, due to
its non-shedding coat, but that trait does not always breed true when it
is part of a designer cross. Also, because breeders of crossbred animals may be less careful about genetic testing and weeding out undesirable traits, certain deleterious dominant genes
may still be passed on to a crossbreed offspring. In an F2 cross,
recessive genetic traits may also return if the parent animals were both
carriers of an undesired trait.
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).
Ethics Genetics is the study of genes and inherited traits and while the
ongoing advancements in this field have resulted in the advancement of
healthcare at multiple levels, ethical considerations have become
increasingly crucial especially alongside. Genetic engineering has
always been a topic of moral debate among bioethicists. Even though the technological advancements in this field present
exciting prospects for biomedical improvement, it also prompts the need
for ethical, societal, and practical assessments to understand its
impact on human biology, evolution, and the environment. Genetic testing, genetic engineering, and stem cell research
are often discussed together due to the interrelated moral arguments
surrounding these topics. The distinction between repairing genes and
enhancing genes is a central idea in many moral debates surrounding
genetic enhancement because some argue that repairing genes is morally
permissible, but that genetic enhancement is not due to its potential to
lead to social injustice through discriminatory eugenics initiatives.
Moral questions related to genetic testing
are often related to duty to warn family members if an inherited
disorder is discovered, how physicians should navigate patient autonomy
and confidentiality with regard to genetic testing, the ethics of
genetic discrimination, and the moral permissibility of using genetic
testing to avoid causing seriously disabled persons to exist, such as
through selective abortion.
The responsibility of public health professionals is to determine
potential exposures and suggest testing for communicable diseases that
require reporting. Public health professionals may encounter disclosure
concerns if the extension of obligatory screening results in genetic
abnormalities being classified as reportable conditions. Genetic data is personal and closely linked to a person's identity.
Confidentiality concerns not only work, health care, and insurance
coverage, but a family's whole genetic test results can be impacted.
Affected individuals may also have their parents, children, siblings,
sisters, and even extended relatives if the condition is either
genetically dominant or carried by them. Moreover, a person's decisions
could change their entire life depending on the outcome of a genetic
test. Results of genetic testing may need to be disclosed in all facets
of a person's life.
Non-invasive prenatal testing (NIPT) can accurately determine the
sex of the fetus at an early stage of gestation, raising concerns about
the potential facilitation of sex-selective termination of pregnancy
(TOP) due to its ease, timing, and precision. Even though the ultrasound
technology can do the same, NIPT is being explored due to its
capability to accurately identify the fetus's sex at an early stage in
pregnancy, with increasing precision as early as 7 weeks' gestation.
This timeframe precedes the typical timing for other sex determination
techniques, such as ultrasound or chorionic villus sampling (CVS).The high early accuracy of NIPT reduces the uncertainty associated with
other methods, such as the aforementioned, leading to more informed
decisions and eliminating the risk of inaccurate results that could
influence decision-making regarding sex-selective TOP. Additionally,
NIPT enables sex-selective TOP in the first trimester, which is more
practical, and allows pregnant women to postpone maternal-fetal bonding.
These considerations may significantly facilitate the pursuit of
sex-selective TOP when NIPT is utilized. Therefore, it is crucial to
examine these ethical concerns within the framework of NIPT adoption.
Ethical issues related to gene therapy and human genetic
enhancement concern the medical risks and benefits of the therapy, the
duty to use the procedures to prevent suffering, reproductive freedom in
genetic choices, and the morality of practicing positive genetics,
which includes attempts to improve normal functions.
In every genetic based study conducted for humanity, studies must
be carried out in accordance with the ethics committee approval
statement, ethical, legal norms and human morality. CAR T cell therapy,
which is intended to be a new treatment aims to change the genetics of T
cells and transform immune system cells that do not recognize cancer
into cells that recognize and fight cancer. it works with the T cell
therapy method, which is arranged with palindromic repeats at certain
short intervals called CRISPR.
All research involving human subjects in healthcare settings must
be registered in a public database before the recruitment of the first
trial. The informed consent statement should include adequate
information about possible conflicts of interest, the expected benefits
of the study, its potential risks, and other issues related to the
discomfort it may involve.
Technological advancements play an integral role in new forms of
human enhancement. While phenotypic and somatic interventions for human
enhancement provide noteworthy ethical and sociological dilemmas,
germline heritable genetic intervention necessitates even more
comprehensive deliberations at the individual and societal levels.
Moral judgments are empirically based and entail evaluating
prospective risk-benefit ratios particularly in the field of
biomedicine. The technology of CRISPR genome editing raises ethical
questions for several reasons. To be more specific, concerns exist
regarding the capabilities and technological constraints of CRISPR
technology. Furthermore, the long-term effects of the altered organisms
and the possibility of the edited genes being passed down to succeeding
generations and having unanticipated effects are two further issues to
be concerned about. Decision-making on morality becomes more difficult
when uncertainty from these circumstances prevents appropriate
risk/benefit assessments.
The potential benefits of revolutionary tools like CRISPR are
endless. For example, because it can be applied directly in the embryo,
CRISPR/Cas9 reduces the time required to modify target genes compared to
gene targeting technologies that rely on the use of embryonic stem (ES)
cells. Bioinformatics tools developed to identify the optimal sequences
for designing guide RNAs and optimization of experimental conditions
have provided very robust procedures that guarantee the successful
introduction of the desired mutation. Major benefits are likely to develop from the use of safe and effective
HGGM, making a precautionary stance against HGGM unethical.
Going forward, many people support the establishment of an
organization that would provide guidance on how best to control the
ethical complexities mentioned above. Recently, a group of scientists
founded the Association for Responsible Research and Innovation in
Genome Editing (ARRIGE) to study and provide guidance on the ethical use
of genome editing.
In addition, Jasanoff and Hurlbut have recently advocated for the
establishment and international development of an interdisciplinary
"global observatory for gene regulation".
Researchers proposed that debates in gene editing should not be
controlled by the scientific community. The network is envisioned to
focus on gathering information from dispersed sources, bringing to the
fore perspectives that are often overlooked, and fostering exchange
across disciplinary and cultural divides.
The interventions aimed at enhancing human traits from a genetic
perspective are emphasized as being contingent upon the understanding of
genetic engineering, and comprehending the outcomes of these
interventions requires an understanding of the interactions between
humans and other living beings. Therefore, the regulation of genetic
engineering underscores the significance of examining the knowledge
between humans and the environment.
To address the ethical challenges and uncertainties arising from
genetic advancements, the development of comprehensive guidelines based
on universal principles has been emphasized as essential. The importance
of adopting a cautious approach to safeguard fundamental values such as
autonomy, global well-being, and individual dignity has been elucidated
when overcoming these challenges.
When contemplating genetic enhancement, genetic technologies
should be approached from a broad perspective, using a definition that
encompasses not only direct genetic manipulation but also indirect
technologies such as biosynthetic drugs. It has been emphasized that
attention should be given to expectations that can shape the marketing
and availability of these technologies, anticipating the allure of new
treatments. These expectations have been noted to potentially signify
the encouragement of appropriate public policies and effective
professional regulations.
Clinical stem cell research must be conducted in accordance with
ethical values. This entails a full respect for ethical principles,
including the accurate assessment of the balance between risks and
benefits, as well as obtaining informed and voluntary participant
consent. The design of research should be strengthened, scientific and
ethical reviews should be effectively coordinated, assurance should be
provided that participants understand the fundamental features of the
research, and full compliance with additional ethical requirements for
disclosing negative findings has been addressed.
Clinicians have been emphasized to understand the role of genomic
medicine in accurately diagnosing patients and guiding treatment
decisions. It has been highlighted that detailed clinical information
and expert opinions are crucial for the accurate interpretation of
genetic variants. While personalized medicine applications are exciting,
it has been noted that the impact and evidence base of each
intervention should be carefully evaluated. The human genome contains
millions of genetic variants, so caution should be exercised and expert
opinions sought when analyzing genomic results.
With the discovery of various types of immune-related disorders,
there is a need for diversification in prevention and treatment.
Developments in the field of gene therapy are being studied to be
included in the scope of this treatment, but of course more research is
needed to increase the positive results and minimize the negative
effects of gene therapy applications. The CRISPR/Cas9 system is also designed as a gene editing technology for
the treatment of HIV-1/AIDS. CRISPR/Cas9 has been developed as the
latest gene editing technique that allows the insertion, deletion and
modification of DNA sequences and provides advantages in the disruption
of the latent HIV-1 virus. However, the production of some vectors for
HIV-1-infected cells is still limited and further studies are needed Being an HIV carrier also plays an important role in the incidence of
cervical cancer. While there are many personal and biological factors
that contribute to the development of cervical cancer, HIV carriage is
correlated with its occurrence. However, long-term research on the
effectiveness of preventive treatment is still ongoing. Early education,
accessible worldwide, will play an important role in prevention. When medications and treatment methods are consistently adhered to, safe
sexual practices are maintained and healthy lifestyle changes are
implemented, the risk of transmission is reduced in most people living
with HIV. Consistently implemented proactive prevention strategies can
significantly reduce the incidence of HIV infections. Education on safe
sex practices and risk-reducing changes for everyone, whether they are
HIV carriers or not, is critical to preventing the disease. However, controlling the HIV epidemic and eliminating the stigma
associated with the disease may not be possible only through a general
AIDS awareness campaign. It is observed that HIV awareness, especially
among individuals in low socio-economic regions, is considerably lower
than the general population. Although there is no clear-cut solution to
prevent the transmission of HIV and the spread of the disease through
sexual transmission, a combination of preventive measures can help to
control the spread of HIV. Increasing knowledge and awareness plays an
important role in preventing the spread of HIV by contributing to the
improvement of behavioral decisions with high risk perception. Genetics plays a pivotal role in disease prevention, offering insights
into an individual's predisposition to certain conditions and paving the
way for personalized strategies to mitigate disease risk. The
burgeoning field of genetic testing and analysis has provided valuable
tools for identifying genetic markers associated with various diseases,
allowing for proactive measures to be taken in disease prevention Disease prevention via genetic testing is made easier as genetic
testing can unveil an individual's genetic susceptibility to certain
diseases, enabling early detection and intervention which can be very
crucial in disease like heritable cancers such and breast and ovarian cancer.Having genetic information can inform the development of precision
medicine approaches and targeted therapies for disease prevention in
general. By identifying genetic factors contributing to disease
susceptibility, such as specific gene mutations associated with
autoimmune disorders, researchers can develop targeted therapies to
modulate the immune response and prevent the onset or progression of
these conditions.
There are many types of neurodegenerative diseases. Alzheimer's
disease is one of the most common one of these diseases and it affects
millions of people worldwide. The CRISPR-Cas9 techniques can be used to
prevent the Alzheimer's disease. For example, it has a potential to
correct the autosomal dominant mutaitons, problematic neurons, restoring
the associated electrophysiological deficits and decreased the Aβ
peptides. Amyotrophic Lateral Sclerosis (ALS) is another highly lethal
neurodegenerative disease. And CRISPR-Cas9 technology is simple and
effective for changinc specific point mutations about ALS. Also with
this technology Chen and his colleagues were found some important
alterations in major indicators of ALS like decreasing in RNA foci,
polypeptides and haplosufficiency.
Some individuals experience immunocompromise,
a condition in which their immune systems are weakened and less
effective in defending against various diseases, including but not
limited to influenza.
This susceptibility to infections can be attributed to a range of
factors, including genetic flaws and genetic diseases such as Severe
Combined Immunodeficiency (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, ). These genetic flaws and diseases can significantly impact the body's
ability to mount an effective immune response, leaving individuals
vulnerable to a wide array of pathogens. However, advancements in gene
therapy research and development have shown promising potential in
addressing these genetic deficiencies however not without associated
challenges
CRISPR technology is a promising tool not only for genetic
disease corrections but also for the prevention of viral and bacterial
infections. Utilizing CRISPR–Cas therapies, researchers have targeted
viral infections like HSV-1, EBV, HIV-1, HBV, HPV, and HCV, with ongoing
clinical trials for an HIV-clearing strategy named EBT-101.
Additionally, CRISPR has demonstrated efficacy in preventing viral
infections such as IAV and SARS-CoV-2 by targeting viral RNA genomes
with Cas13d, and it has been used to sensitize antibiotic-resistant S.
aureus to treatment through Cas9 delivered via bacteriophages.
Advancements in gene editing and gene therapy hold promise for
disease prevention by addressing genetic factors associated with certain
conditions. Techniques like CRISPR-Cas9 offer the potential to correct
genetic mutations associated with hereditary diseases, thereby
preventing their manifestation in future generations and reducing
disease burden. 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.
Despite existing evidence of CRISPR technology, advancements in
the field persist in reducing limitations. Researchers developed a new,
gentle gene editing method for embryos using nanoparticles and peptide
nucleic acids. Delivering editing tools without harsh injections, the
method successfully corrected genes in mice without harming development.
While ethical and technical questions remain, this study paves the way
for potential future use in improving livestock and research animals,
and maybe even in human embryos for disease prevention or therapy.
Informing prospective parents about their susceptibility to
genetic diseases is crucial. Pre-implantation genetic diagnosis also
holds significance for disease prevention by inheritance, as whole
genome amplification and analysis help select a healthy embryo for
implantation, preventing the transmission of a fatal metabolic disorder
in the family.
Genetic human enhancement emerges as a potential frontier in
disease prevention by precisely targeting genetic predispositions to
various illnesses. Through techniques like CRISPR, specific genes
associated with diseases can be edited or modified, offering the
prospect of reducing the hereditary risk of conditions such as cancer,
cardiovascular disorders, or neurodegenerative diseases. This approach
not only holds the potential to break the cycle of certain genetic
disorders but also to influence the health trajectories of future
generations.
Furthermore, genetic enhancement can extend its impact by
focusing on fortifying the immune system and optimizing overall health
parameters. By enhancing immune responses and fine-tuning genetic
factors related to general well-being, the susceptibility to infectious
diseases can be minimized. This proactive approach to health may
contribute to a population less prone to ailments and more resilient in
the face of environmental challenges.
However, the ethical dimensions of genetic manipulation cannot be
overstated. Striking a delicate balance between scientific progress and
ethical considerations is imperative. Robust regulatory frameworks and
transparent guidelines are crucial to ensuring that genetic human
enhancement is utilized responsibly, avoiding unintended consequences or
potential misuse. As the field advances, the integration of ethical,
legal, and social perspectives becomes paramount to harness the full
potential of genetic human enhancement for disease prevention while
respecting individual rights and societal values.
Overall, the technology requires improvements in effectiveness,
precision, and applications. Immunogenicity, off-target effects,
mutations, delivery systems, and ethical issues are the main challenges
that CRISPR technology faces. The safety concerns, ethical
considerations, and the potential for misuse underscore the need for
careful and responsible exploration of these technologies. CRISPR-Cas9 technology offers so much on disease prevention and
treatment yet its future aspects, especially those that affect the next
generations, should be investigated strictly.
Modification of human genes in order to treat genetic diseases is referred to as gene therapy.
Gene therapy is a medical procedure that involves inserting genetic
material into a patient's cells to repair or fix a malfunctioning gene
in order to treat hereditary illnesses. Between 1989 and December 2018,
over 2,900 clinical trials of gene therapies were conducted, with more than half of them in phase I. Since that time, many gene therapy based drugs became available, such as Zolgensma and Patisiran. Most of these approaches utilize viral vectors, such as adeno-associated viruses (AAVs), adenoviruses (AV) and lentiviruses (LV), for inserting or replacing transgenesin vivo or ex vivo.
In 2023, nanoparticles that act similarly to viral vectors were created. These nanoparticles, called bioorthgonal engineered virus-like recombinant biosomes, display strong and rapid binding capabilities to LDL receptors on cell surfaces, allowing them to enter cells efficiently and deliver genes to specific target areas, such as tumor and arthritic tissues.
RNA interference-based agents, such as zilebesiran, contain siRNA which binds with mRNA of the target cells, modifying gene expression.
Many diseases are complex and cannot be effectively treated by simple
coding sequence-targeting strategies. CRISPR/Cas9 is one technology
that targets double strand breaks in the human genome, modifying genes
and providing a quick way to treat genetic disorders. Gene treatment
employing the CRISPR/Cas genome editing method is known as
CRISPR/Cas-based gene therapy. Mammalian cells can be genetically
modified using the straightforward, affordable, and extremely specific
CRISPR/Cas method. It can help with single-base exchanges,
homology-directed repair, and non-homologous end joining. The primary
application is targeted gene knockouts, involving the disruption of
coding sequences to silence deleterious proteins. Since the development
of the CRISPR-Cas9 gene editing method between 2010 and 2012, scientists
have been able to alter genes by making specific breaks in their DNA.
This technology has many uses, including genome editing and molecular diagnosis.
Genetic engineering has undergone a revolution because to
CRISPR/Cas technology, which provides a flexible framework for building
disease models in larger animals. This breakthrough has created new
opportunities to evaluate possible therapeutic strategies and comprehend
the genetic foundations of different diseases. But in order to fully
realize the promise of CRISPR/Cas-based gene therapy, a number of
obstacles must be removed. Improving CRISPR/Cas systems' editing
precision and efficiency is one of the main issues. Although this
technology makes precise gene editing possible, reducing off-target
consequences is still a major challenge. Unintentional genetic changes
resulting from off-target modifications may have unanticipated effects
or difficulties. Using enhanced guide RNA designs, updated Cas proteins,
and cutting-edge bioinformatics tools, researchers are actively
attempting to improve the specificity and reduce off-target effects of
CRISPR/Cas procedures. Moreover, the effective and specific delivery of
CRISPR components to target tissues presents another obstacle. Delivery
systems must be developed or optimized to ensure the CRISPR machinery
reaches the intended cells or organs efficiently and safely. This
includes exploring various delivery methods such as viral vectors,
nanoparticles, or lipid-based carriers to transport CRISPR components
accurately to the target tissues while minimizing potential toxicity or
immune responses.
Despite recent progress, further research is needed to develop
safe and effective CRISPR therapies. CRISPR/Cas9 technology is not
actively used today, however there are ongoing clinical trials of its
use in treating various disorders, including sickle cell disease, human
papillomavirus (HPV)-related cervical cancer, COVID-19 respiratory
infection, renal cell carcinoma, and multiple myeloma.
Gene therapy has emerged as a promising field in medical science, aiming to address and treat various genetic diseases by modifying human genes.
The process involves the introduction of genetic material into a
patient's cells, with the primary goal of repairing or correcting
malfunctioning genes that contribute to hereditary illnesses.
This innovative medical procedure has seen significant advancements and
a growing number of clinical trials since its inception.
Between 1989 and December 2018, more than 2,900 clinical trials
of gene therapies were conducted, with over half of them reaching the
phase I stage. Over the years, several gene therapy-based drugs have
been developed and made available to the public, marking important
milestones in the treatment of genetic disorders. Examples include Zolgensma and Patisiran, which have demonstrated efficacy in addressing specific genetic conditions.
The majority of gene therapy approaches leverage viral vectors,
such as adeno-associated viruses (AAVs), adenoviruses (AV), and
lentiviruses (LV), to facilitate the insertion or replacement of
transgenes either in vivo or ex vivo. These vectors serve as delivery
vehicles for introducing the therapeutic genetic material into the
patient's cells.
A notable development in 2023 was the creation of nanoparticles
designed to function similarly to viral vectors. These bioorthogonal
engineered virus-like recombinant biosomes represent a novel approach to
gene delivery. They exhibit robust and rapid binding capabilities to
low-density lipoprotein (LDL) receptors on cell surfaces, enhancing
their efficiency in entering cells. This capability enables the targeted
delivery of genes to specific areas, such as tumor and arthritic
tissues. This advancement holds the potential to enhance the precision
and effectiveness of gene therapy, minimizing off-target effects and
improving overall therapeutic outcomes.
In addition to viral vector and nanoparticle-based approaches,
RNA interference (RNAi) has emerged as another strategy in gene therapy.
Agents like zilebesiran utilize small interfering RNA (siRNA) that
binds with the messenger RNA (mRNA)
of target cells, effectively modifying gene expression. This RNA
interference-based approach provides a targeted and specific method for
regulating gene activity, presenting further opportunities for treating genetic disorders.
The continuous evolution of gene therapy techniques,
along with the development of innovative delivery systems and
therapeutic agents, underscores the ongoing commitment of the scientific
and medical communities to advance the field and provide effective
treatments for a wide range of genetic diseases.
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. Therefore, this technology, which is a subfield of genetic engineering
commonly referred to as gene doping in sports, has been prohibited due
to its potential risks. The primary objective of gene doping is to aid individuals with medical
conditions. However, athletes, cognizant of its associated health
risks, resort to employing this method in pursuit of enhanced athletic
performance. The prohibition of the indiscriminate use of gene doping in
sports has been enforced since the year 2003, pursuant to the decision
taken by the World Anti-Doping Agency (WADA). A study conducted in 2011 underscored the significance of addressing
issues related to gene doping and highlighted the importance of promptly
comprehending how gene doping in sports and exercise medicine could
impact healthcare services by elucidating its potential to enhance
athletic performance. The article elucidates, according to the World
Anti-Doping Agency (WADA), how gene doping poses a threat to the
fairness of sports. Additionally, the paper delves into health concerns
that may arise as a consequence of the utilization of gene doping solely
for the purpose of enhancing sports performance. The misuse of gene doping to enhance athletic performance constitutes
an unethical practice and entails significant health risks, including
but not limited to cancer, viral infections, myocardial infarction,
skeletal damage, and autoimmune complications. In addition, gene doping
may give rise to various health issues, such as excessive muscle
development leading to conditions like hypertonic cardiomyopathy, and
render bones and tendons more susceptible to injuries Several genes such as EPO, IGF1, VEGFA, GH, HIFs, PPARD, PCK1, and
myostatins are prominent choices for gene doping. Particularly in gene
doping, athletes employ substances such as antibodies against myostatin
or myostatin blockers. These substances contribute to the augmentation
of the athletes' mass, facilitation of increased muscle development, and
enhancement of strength. However, the primary genes utilized for gene
doping in humans may lead to complications such as excessive muscle
growth, which can adversely impact the cardiovascular system and
increase the likelihood of injuries. However, due to insufficient awareness of these risks, numerous
athletes resort to employing gene doping for purposes divergent from its
genuine intent. Within the realm of athlete health, sports ethics and
the ethos of fair play, scientists have developed various technologies
for the detection of gene doping. Although in its early years the
technology used wasn’t reliable, more extensive research has been done
for better techniques to uncover gene doping instances that have been
more successful. In the beginning, scientist resorted to techniques such
as PCR in its various forms. This was not successful due to the fact
that such technologies rely on exon-exon junctions in the DNA. This
leads to a lack of precision in its detection as results can be easily
tampered using misleading primers and gene doping would go undetected. With the emerge of new technologies, more recent studies utilized Next
Generation Sequencing (NGS) as a method of detection. With the help of
bioinformatics, this technology surpassed previous sequencing techniques
in its in-depth analysis of DNA make up. Next Generation Sequencing
(NGS) focuses on using an elaborate method of analyzing sample sequence
and comparing it to a pre-existing reference sequence from a gene
database. This way, primer tampering is not possible as the detection is
on a genomic level. Using bioinformatic visualizing tools, data can be
easily read and sequences that do not align with reference sequence can
be highlighted.[66][67]
Most recently, One of the high-efficiency gene doping analysis methods
conducted in the year 2023, leveraging cutting-edge technology, is HiGDA
(High-efficiency Gene Doping Analysis), which employs CRISPR/deadCas9
technology.
The ethical issues concerning gene doping have been present long
before its discovery. Although gene doping is relatively new, the
concept of genetic enhancement of any kind has always been subject to
ethical concerns. Even when used in a therapeutic manner, gene therapy
poses many risks due to its unpredictability among other reasons.
Factors other than health issues have raised ethical questions as well.
These are mostly concerned with the hereditary factor of these
therapies, where gene editing in some cases can be transmitted to the
next generation with higher rates of unpredictability and risks in
outcomes. For this reason, non-therapeutic application of gene therapy can be seen as a riskier approach to a non-medical concern.[70]
In a study, from history to today, human beings have always been
in competition. While in the past warriors competed to be stronger in
wars, today there is competition to be successful in every field, and it
is understood that this psychology is a phenomenon that has always
existed in human history until today. It is known that although an
athlete has genetic potential, he cannot become a champion if he does
not comply with the necessary training and lifestyle. However, as
competition increases, both more physical training and more mental
performance are needed. Just as warriors in history used some herbal
cures to look stronger and more aggressive, it is a fact that today,
athletes resort to doping methods to increase their performance.
However, this situation is against sports ethics because it does not
comply with the morality and understanding of the game.
One of the negative effects is the risk of cancer, and as a
positive effect is taking precautions against certain pathological
conditions.Altering genes could lead to unintended and unpredictable
changes in the body, potentially causing unforeseen health issues.
Further effects of gene doping in sports is the constant fight against
drugs not approved by the World Anti doping agency and unfairness
regarding athletes that take drugs and don't. The long-term health
consequences of gene doping may not be fully understood, and athletes
may face health problems later in life.
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).
The exploration of challenges in understanding the effects of gene
alterations on phenotypes, particularly within natural genetic
diversity, is highlighted. Emphasis is placed on the potential of
systems biology and advancements in genotyping/phenotyping
technologies for studying complex traits. Despite progress, persistent
difficulties in predicting the influence of gene alterations on
phenotypic changes are acknowledged, emphasizing the ongoing need for
research in this area.
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.
- Phenotypic Impacts of CRISPR-Cas9 Editing in Mice Targeting the Tyr Gene:
In a comprehensive CRISPR-Cas9
study on gene editing, the Tyr gene in mice was targeted, seeking to
instigate genetic alterations. The analysis found no off-target effects
across 42 subjects, observing modifications exclusively at the intended
Tyr locus. Though specifics were not explicitly discussed, these
alterations may potentially influence non-defined aspects, such as coat
color, emphasizing the broader potential of gene editing in inducing
diverse phenotype changes.
Also changes in the myostatin gene may alter appearance.
Significant quantitative genetic discoveries were made in the 1970s and 1980s, going beyond estimating heritability. However, issues such as The Bell Curve resurfaced, and by the 1990s, scientists recognized the importance of genetics for behavioral traits such as intelligence. The American Psychological Association's Centennial Conference in 1992 chose behavioral genetics as a theme for the past, present, and future of psychology. Molecular genetics synthesized, resulting in the DNA revolution and behavioral genomics, as quantitative genetic discoveries slowed. Individual behavioral differences can now be predicted early thanks to the behavioral sciences'
DNA revolution. The first law of behavioral genetics was established in
1978 after a review of thirty twin studies revealed that the average
heritability estimate for intelligence was 46%. Behavior may also be modified by genetic intervention. Some people may be aggressive, selfish, and may not be able to
function well in society. Mutations in GLI3 and other patterning genes
have been linked to HH etiology, according to genetic research.
Approximately 50%-80% of children with HH have acute wrath and violence,
and the majority of patients have externalizing problems. Epilepsy may
be preceded by behavioral instability and intellectual incapacity. 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 has been a great anticipation of gene editing technology to modify genes and regulate our biology
since the invention of recombinant DNA technology. These expectations,
however, have mostly gone unmet. Evaluation of the appropriate uses of
germline interventions in reproductive medicine should not be based on
concerns about enhancement or eugenics, despite the fact that gene
editing research has advanced significantly toward clinical application.
Cystic fibrosis (CF) is a hereditary disease caused by mutations in the Cystic fibrosis transmembrane conductance regulator (CFTR)
gene. While 90% of CF patients can be treated, current treatments are
not curative and do not address the entire spectrum of CFTR mutations.
Therefore, a comprehensive, long-term therapy is needed to treat all CF patients once and for all. CRISPR/Casgene editing technologies are being developed as a viable platform for genetic treatment. However, the difficulties of delivering enough CFTR gene and sustaining expression in the lungs has hampered gene therapy's efficacy. Recent technical breakthroughs, including as viral and non-viral vector transport, alternative nucleic acid technologies, and new technologies like mRNA and CRISPR gene editing, have taken use of our understanding of CF biology and airway epithelium.
Human gene transfer has held the promise of a lasting remedy to hereditary illnesses such as cystic fibrosis (CF)
since its conception and use. The emergence of sophisticated
technologies that allow for site-specific alteration with programmable
nucleases has greatly revitalized the area of gene therapy. 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.
Some studies show that our genes may affect some of our
behaviors. For example, some genes may follow our state of stagnation,
while others may be responsible for our bad habits. To give an example,
the MAOA (Mono oxidase A) gene, the feature of this gene affects the
release of hormones such as serotonin, epinephrine and dopamine and
suppresses them. It prevents us from reacting in some situations and
from stopping and making quick decisions in other situations, which can
cause us to make wrong decisions in possible bad situations. As a result
of some research, mood states such as aggression, feelings of
compassion and irritability can be observed in people carrying this
gene. Additionally, as a result of research conducted on people carrying
the MAOA gene, this gene can be passed on genetically from parents, and
mutations can also develop due to later epigenetic reasons. If we talk
about epigenetic reasons, children of families growing up in bad
environments begin to implement whatever they see from their parents.
For this reason, those children begin to exhibit bad habits or behaviors
such as irritability and aggression in the future.
In 2022, the People's Liberation Army Academy of Military
Sciences reported a notable experiment where military scientists
inserted a gene from the tardigrade into human embryonic stem cells. This experiment aimed to explore the potential enhancement of soldiers' resistance to acute radiation syndrome,
thereby increasing their ability to survive nuclear fallout. This
development reflects the intersection of genetic engineering and military research, with a focus on bioenhancement for military personnel.
CRISPR/Cas9
technologies have garnered attention for their potential applications
in military contexts. Various projects are underway, including those
focused on protecting soldiers from specific challenges. For instance,
researchers are exploring the use of CRISPR/Cas9 to provide protection
from frostbite, reduce stress levels, alleviate sleep deprivation, and enhance strength and endurance. The Defense Advanced Research Projects Agency (DARPA) is actively involved in researching and developing these technologies. One of their projects aims to engineer human cells to function as nutrient factories, potentially optimizing soldiers' performance and resilience in challenging environments.
Additionally, military researchers are conducting animal trials
to explore the prophylactic treatment for long-term protection against
chemical weapons of mass destruction. This involves using non-pathogenic
AAV8 vectors to deliver a candidate catalytic bioscavenger, PON1-IF11,
into the bloodstream of mice. These initiatives underscore the broader exploration of genetic and molecular interventions to enhance military capabilities and protect personnel from various threats.
In the realm of bioenhancement, concerns have been raised about the use of dietary supplements and other biomedical
enhancements by military personnel. A significant portion of American
special operations forces reportedly use dietary supplements to enhance
performance, but the extent of the use of other bioenhancement methods,
such as steroids, human growth hormone, and erythropoietin, remains
unclear. The lack of completed safety and efficacy testing for these
bioenhancements raises ethical and regulatory questions. This concern is
not new, as issues surrounding the off-label use of products like pyridostigmine bromide and botulinum toxoid vaccine during the Gulf War, as well as the DoD's Anthrax Vaccine Immunization Program in 1998, have prompted discussions about the need for thorough FDA approval for specific military applications.
The intersection of genetic engineering, CRISPR/Cas9
technologies, and military research introduces complex ethical
considerations regarding the potential augmentation of human
capabilities for military purposes. Striking a balance between
scientific advancements, ethical standards, and regulatory oversight
over classified projects remain crucial as these technologies continue
to evolve.
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.
