BIOLOGY

PROJECT
ON

HUMAN GENETIC
MODIFICATION
PRESENTED BY:
M.GHAJHA PRIYA
XII-A1
 BONAFIDE CERTIFICATE

This is to certify that this is a Bonafide

Record of Biology Project work done by

M.Ghajha Priya of Class XII and section A1
during the year 2024-2025 in Velammal
Bodhi Campus, Anuppanadi, Madurai.

Teacher Incharge, Principal,

Internal Examiner, External Examiner,

 ACKNOWLEDGEMENT
First of all, I wholeheartedly thank the
almighty who blessed me with very
supportive people around me.
I would like to express my special thanks of
gratitude to my Biology Teachers
Mr.Rajasekaran and Mr.Karuppasamy for
their guidance and support to complete this
project on time.
I would like to extend my gratitude to the
Principal Sir Mr.Balamurugan for providing
timely support and required facilities.
I thank our Chairman of Velammal Bodhi
Campus, Anuppanadi, Madurai for providing
us ample facilities to learn many things
while doing this investigatory project and to
complete it on time.
Finally, I would like to thank my Parents
who extended their helping hands to finish
and finalise this project.
 INTRODUCTION

Human genetic modification (or “gene editing”) can

be used in two very different ways. Somatic genome
editing changes the genes in a patient’s cells to treat a
medical condition. A few gene therapies are
approaching clinical use but remain extraordinarily
expensive.
By contrast, heritable genome editing would change
genes in eggs, sperm, or early embryos to try to control
the traits of a future child. Such alterations would affect
every cell of the resulting person and all subsequent
generations.
For safety, ethical, and social reasons, heritable genome
editing is widely considered unacceptable.
It is prohibited in 70 countries and by a binding
international treaty. Nevertheless, in 2018 one scientist
announced the birth of twins whose embryos he had
edited. This reckless experiment intensified debate
between advocates of heritable genome editing and
those concerned it could exacerbate inequality and lead
to a new, market-based eugenics.
Genome editing is a way of making changes to specific
parts of a genome. Scientists have been able to alter
DNA since the 1970s, but in recent years, they have
developed faster, cheaper, and more precise methods to
add, remove, or change genes in living organisms.
Researchers are working to develop therapies that use
gene editing to treat children or adults for a range of
conditions, including sickle cell, hemophilia, and some
forms of cancer and blindness.
Since 2015, a few laboratories have been experimenting
with a far more controversial use of CRISPR: editing
the genomes of early human embryos, eggs, and sperm.
If edited embryos are used to start a pregnancy, the
changes affect every cell in the body of any resulting
child, that child’s offspring, their offspring, and so
on. Dozens of countries already prohibit any attempt to
start a pregnancy with edited embryos, yet some
scientists seem eager to proceed.
In November 2018, researcher He Jiankui from
Shenzhen, China announced the birth of the first gene-
edited babies: twin girls publicly referred to as Lulu
and Nana. In a reckless and widely
condemned experiment, He had edited the DNA of two
embryos and used them to start a pregnancy. The babies
were born prematurely and their current health status
is unknown.
These utterly unethical experiments have pushed the
issue of human genome editing to the forefront of
media, scientific, and public discussion and debate. Any
discussion of how we might use this technology in the
future needs to consider the serious societal
consequences of human genome editing. This includes
examining the rise of vast economic inequalities and the
resurgence of overt xenophobia and racism in many
parts of the world. It also includes acknowledging our
eugenic histories and the present-day systemic
oppression of women, people of color, Indigenous
people, LGBTQ people, and people with disabilities,
particularly as they relate to reproduction and ideas
about who is “fit” to reproduce.
Human genome editing is not just a scientific issue. It
is a political and social justice issue that intersects
with the concerns of multiple movements, including
disability rights, LGBTQ rights, reproductive rights and
justice, racial justice, environmental justice, and health
justice. Read on to learn more about human genome
editing and why everyone should have a say in the
decisions we make about whether and how to use this
powerful technology.
 What is CRISPR?

CRISPR is a gene editing technology that allows

scientists to make changes to the DNA of living
organisms more precisely and inexpensively than before.
CRISPR stands for clustered regularly interspaced
palindromic repeats. These segments of DNA occur
naturally in bacteria, where they store information that
helps recognize invading viruses. Associated enzymes,
such as Cas9, then cut viral DNA out of the bacterial
genes.
Scientists discovered that they can adapt CRISPR-Cas
molecules to search for a specific DNA sequence and
cut precisely at that point — not just in bacteria, but in
plant, animal, and human cells, too. They can also
provide a new DNA sequence for the cell to use when it
repairs the cut.
CRISPR-Cas is often compared to the “find and
replace” function in a word processor, but this metaphor
of gene “editing” can make it sound more precise than
it actually is. CRISPR sometimes mis-recognizes a
DNA sequence that is similar to the one it’s looking for
and cuts in the wrong place, causing “off-target
mutations.” Other times it might cut in the right place,
but cause mistakes, or “indels,” where DNA is
incorrectly inserted or deleted.
 Gene Therapy: Changing genomes to treat
disease
There are two distinct ways gene editing might be used
in humans. Gene therapy, or somatic gene editing,
changes the DNA in cells of an adult or child to treat
disease, or even to try to enhance that person in some
way. The changes made in these somatic (or body) cells
would be permanent but would only affect the person
treated. One way this is already being done is by editing
a person’s immune cells to help them better fight
cancer. Clinical trials will soon be underway to use
CRISPR to edit blood cells as a treatment for sickle cell
anemia and other blood disorders. Gene therapy raises
many of the same social and ethical issues as other
high-tech medical treatments, including ethical research
practices, safety and effectiveness, unequal access
to expensive treatments, and how we allocate
resources, but is widely supported as a promising way
to treat disease.
In 1990,a 4-year-old girl became the first gene therapy
success story. She was born with a severe combined
immunodeficiency (SCID) due to lack of the enzyme
adenosine deaminase (ADA). Without ADA, her T cells
died off, leaving her unable to fight infections.
Injections of a synthetic ADA enzyme helped, but only
temporarily.
The first paper, in 1984, showing that a virus could
insert genes into cells.
Doctors decided to deliver a healthy ADA gene into her
blood cells, using a disabled virus that cannot spread in
the body. Their success spurred more trials in the 1990s
for the same form of SCID. Now in her 30s, de Silva is
active in the rare disease community.
European researchers in the 1990s focused on SCID-
X1, another form of SCID linked to the X chromosome.
They reported the first cures in 2000, but within several
years, five of the 20 treated children developed
cancer. The viral vector that delivered the gene to their
T cells had also activated an oncogene, triggering
leukemia.
The U.S. saw another early setback: the 1999 death of
18-year-old Jesse Gelsinger, after receiving gene
therapy for a rare metabolic disorder. In his case, the
viral vector caused a fatal immune response.
Gene therapy came to a halt.
 Germline Editing: Changing the genomes of
future generations

But there is a much more controversial way that human

gene editing could be used. In germline modification,
gene editing would change the DNA of embryos, eggs,
or sperm. Because germline DNA is passed down to all
future generations, any changes — whether they had
beneficial or harmful effects — would be as well. Some
have proposed that germline editing could be used to
prevent inherited diseases, but this would
carry unacceptably serious safety, ethical, and social
risks. And it’s unneeded, since we already have safe
and effective ways to prevent passing on an inherited
disease. People at risk can use preimplantation genetic
diagnosis (PGD), a way to screen embryos created
through in vitro fertilization (IVF) and select one that is
unaffected; this allows parents to have a genetically
related child without passing on an inherited disease.
PGD certainly raises its own ethical questions,
particularly around disability rights and justice, but it
poses fewer safety and societal risks than germline
editing would.
Recently, the US National Academy of Sciences and
National Academy of Medicine released their report on
recommendations for human genome editing. The
committee that authored the report comprised research
scientists, clinicians, regulatory agents and bioethicists,
and the goal was to reach consensus guidelines for
responsible applications of human genome editing in
the laboratory and the clinic. This report clearly lays out
the scientific and social implications of human genome
editing and proposes guiding principles for its use. We
strongly support the advance of science while at the
same time agreeing that it is prudent to proceed with
caution, particularly with regard to rapidly developing
technologies that have the potential to have a profound
impact on research, medicine and society.

The capacity to edit genes has existed for decades, and

genetic modification is common practice in the
laboratory. The reason for the heightened attention and
concern now is that technological advances have
enabled the precise editing of genomes at
unprecedented speed and scale. Zinc-finger nucleases,
TALENs and, now, the CRISPR–Cas9 system have
revolutionized scientific discovery. As such, the
applications of these powerful tools must be thoroughly
discussed and debated. While applications of genome
editing to laboratory organisms, crop plants, domestic
animals and disease vectors come with different
considerations of varying complexity and consequence,
the use of genomic editing to introduce potentially
heritable alterations in humans should be in a separate
category, subject to greater scrutiny and regulation.

We wrote in these pages last year (Nat. Genet. 48, 103,

2016) that genome editing in crop plants should be
regulated on the basis of the end product, not the
process by which genetic mutations are introduced.
Genome editing is merely a faster and more accurate
method than classical breeding and is not fundamentally
different. While it may be an appropriate approach for
plants and domestic animals, a distinct line can be
drawn between these applications and ones involving
genetic modification of the human germ line, which
justify greater oversight. Although there are regulations
for gene therapy, the exceptional versatility and
precision of genome editing elevate the possibilities of
not only what modifications can be made but also how
quickly and accurately they can be introduced.
Unintended or long-term consequences of editing
humans or human germ cells and embryos have the
potential to seriously affect not only the subjects
themselves, but also their progeny.

We agree with the National Academies'

recommendations that somatic genome editing should
fall under existing regulations that apply to human
clinical research. Correcting mutation through the germ
line is different in kind, not degree. This is due to the
fact that changes introduced into germ cells are
heritable through subsequent generations. Therefore,
these alterations have effects that go beyond a single
individual. Data are lacking on the long-term
consequences of germline genome editing. Off-target
effects and lack of consent are two of the main issues to
consider. The National Academies have recommended
that germline genome editing trials be permitted, but
only when compliant with all standards for human
clinical trials along with additional rigorous oversight.
They stipulate that such research be restricted to the
treatment or prevention of disease. Any other
application (for example, genetic 'enhancement') should
not be allowed to proceed at this time.

This committee strongly recommended that the public

be informed of progress already made in human
genome editing as well as any future developments. We
think it is especially important for scientists to make
public education and outreach an integral part of their
research and to have discussions with relevant parties,
including members of the public, regulatory agencies
and medical professionals. It is critical that the social
license to operate these technologies for therapy not be
infringed by premature experimentation on heritable
genome engineering for proof of principle or academic
priority. The future safety of germline edits is an
important area for research that we think can readily be
explained to the public.

Further, there are currently few genetic arguments for

the necessity of correcting the genetic material of future
generations given pre-implantation diagnosis of
monogenic conditions. Therefore, we think it is
imperative to discuss future concepts of genome editing
that could be considered acceptable therapies. One
might discuss a panel of deleterious mutations lacking
compensating selective advantages that would be
justified for multiplex removal from all in vitro–
fertilized (IVF) embryos. If germline editing technology
could achieve this end routinely and safely, without
genotypic discrimination, it would then be as ready for
implementation as a panel of recommended
vaccinations.

One can be supportive of scientific advance and at the

same time advise reasonable caution in the adoption of
powerful new technologies. Much more needs to be
known about the safety and consequences of human
germline genome editing before it can be considered for
medical application. Additionally, the motivation for
adopting the technology, together with legal and ethical
issues, needs to be thoroughly discussed and revisited
as more information becomes available. Allowing for
clinical trials to proceed in this area, under strict
oversight and without regional loopholes in legislation,
will help answer some outstanding questions and usher
in this new era with forethought and responsibility.
 THE HUMAN GENOME PROJECT

Ofcourse, genetic modification in humans would have

been a much difficult if it weren’t for the human
genome project.
The Human Genome Project (HGP) was an
international scientific research project with the goal of
determining the base pairs that make up human DNA,
and of identifying, mapping and sequencing all of
the genes of the human genome from both a physical
and a functional standpoint. It started in 1990 and was
completed in 2003. It remains the world's largest
collaborative biological project. Planning for the project
began in 1984 by the US government, and it officially
launched in 1990. It was declared complete on April 14,
2003, and included about 92% of the genome. Level
"complete genome" was achieved in May 2021, with
only 0.3% of the bases covered by potential issues. The
final gapless assembly was finished in January 2022.
Funding came from the United States government
through the National Institutes of Health (NIH) as well
as numerous other groups from around the world. A
parallel project was conducted outside the government
by the Celera Corporation, or Celera Genomics, which
was formally launched in 1998. Most of the
government-sponsored sequencing was performed in
twenty universities and research centres in the United
States, the United Kingdom, Japan, France, Germany,
and China, working in the International Human
Genome Sequencing Consortium (IHGSC).
The Human Genome Project originally aimed to map
the complete set of nucleotides contained in a
human haploid reference genome, of which there are
more than three billion. The genome of any given
individual is unique; mapping the human
genome involved sequencing samples collected from a
small number of individuals and then assembling the
sequenced fragments to get a complete sequence for
each of the 23 human chromosome pairs (22 pairs of
autosomes and a pair of sex chromosomes, known as
allosomes). Therefore, the finished human genome is a
mosaic, not representing any one individual. Much of
the project's utility comes from the fact that the vast
majority of the human genome is the same in all
humans.
The Human Genome Project was a 13 year-long
publicly funded project initiated in 1990 with the
objective of determining the DNA sequence of the
entire euchromatic human genome within 13 years.The
idea of such a project originated in the work of Ronald
A. Fisher, whose work is also credited with later
initiating the project.
In May 1985, Robert Sinsheimer organized a workshop
at the University of California, Santa Cruz, to discuss
the feasibility of building a systematic reference
genome using gene sequencing technologies. In March
1986, the Santa Fe Workshop was organized by Charles
DeLisi and David Smith of the Department of Energy's
Office of Health and Environmental Research
(OHER). At the same time Renato Dulbecco, President
of the Salk Institute for Biological Studies, first
proposed the concept of whole genome sequencing in
an essay in Science. The published work, titled "A
Turning Point in Cancer Research: Sequencing the
Human Genome", was shortened from the original
proposal of using the sequence to understand the
genetic basis of breast cancer. James Watson, one of the
discoverers of the double helix shape of DNA in the
1950s, followed two months later with a workshop held
at the Cold Spring Harbor Laboratory. Thus the idea for
obtaining a reference sequence had three independent
origins: Sinsheimer, Dulbecco and DeLisi. Ultimately it
was the actions by DeLisi that launched the project.
The fact that the Santa Fe Workshop was motivated and
supported by a federal agency opened a path, albeit a
difficult and tortuous one, for converting the idea into
public policy in the United States. In a memo to the
Assistant Secretary for Energy Research Alvin
Trivelpiece, then-Director of the OHER Charles DeLisi
outlined a broad plan for the project. This started a long
and complex chain of events which led to approved
reprogramming of funds that enabled the OHER to
launch the project in 1986, and to recommend the first
line item for the HGP, which was in President Reagan's
1988 budget submission, and ultimately approved by
Congress. Of particular importance in congressional
approval was the advocacy of New Mexico
Senator Pete Domenici, whom DeLisi had
befriended. Domenici chaired the Senate Committee on
Energy and Natural Resources, as well as the Budget
Committee, both of which were key in the DOE budget
process. Congress added a comparable amount to the
NIH budget, thereby beginning official funding by both
agencies.
Trivelpiece sought and obtained the approval of
DeLisi's proposal from Deputy Secretary William Flynn
Martin. This chart was used by Trivelpiece in the spring
of 1986 to brief Martin and Under Secretary Joseph
Salgado regarding his intention to reprogram $4 million
to initiate the project with the approval of John S.
Herrington. This reprogramming was followed by a line
item budget of $13 million in the Reagan
administration's 1987 budget submission to Congress. It
subsequently passed both Houses. The project was
planned to be completed within 15 years.
In 1990, the two major funding agencies, DOE and
the National Institutes of Health, developed a
memorandum of understanding in order to coordinate
plans and set the clock for the initiation of the Project to
1990. At that time, David J. Galas was Director of the
renamed "Office of Biological and Environmental
Research" in the U.S. Department of Energy's Office of
Science and James Watson headed the NIH Genome
Program. In 1993, Aristides Patrinos succeeded Galas
and Francis Collins succeeded Watson, assuming the
role of overall Project Head as Director of the NIH
National Center for Human Genome Research (which
would later become the National Human Genome
Research Institute). A working draft of the genome was
announced in 2000 and the papers describing it were
published in February 2001. A more complete draft was
published in 2003, and genome "finishing" work
continued for more than a decade after that.
The $3 billion project was formally founded in 1990 by
the US Department of Energy and the National
Institutes of Health, and was expected to take 15 years.
In addition to the United States, the
international consortium comprised geneticists in the
United Kingdom, France, Australia, China, and myriad
other spontaneous relationships. The project ended up
costing less than expected, at about $2.7 billion
(equivalent to about $5 billion in 2021).
Two technologies enabled the project: gene
mapping and DNA sequencing. The gene mapping
technique of restriction fragment length
polymorphism (RFLP) arose from the search for the
location of the breast cancer gene by Mark Skolnick of
the University of Utah, which began in 1974. Seeing a
linkage marker for the gene, in collaboration
with David Botstein, Ray White and Ron
Davis conceived of a way to construct a genetic
linkage map of the human genome. This enabled
scientists to launch the larger human genome effort.
Because of widespread international cooperation and
advances in the field of genomics (especially
in sequence analysis), as well as parallel advances in
computing technology, a 'rough draft' of the genome
was finished in 2000 (announced jointly by U.S.
President Bill Clinton and British Prime Minister Tony
Blair on June 26, 2000). This first available rough
draft assembly of the genome was completed by the
Genome Bioinformatics Group at the University of
California, Santa Cruz, primarily led by then-graduate
student Jim Kent and his advisor David Haussler.
Ongoing sequencing led to the announcement of the
essentially complete genome on April 14, 2003, two
years earlier than planned. In May 2006, another
milestone was passed on the way to completion of the
project when the sequence of the very last
chromosome was published in Nature.
Understanding the Social and Ethical Risks
New technologies often raise ethical questions about
their unknown risks and benefits. These questions
become especially tricky — and essential — when we
are talking about something like human germline
editing, which affects future generations who obviously
can’t consent to the changes being made to their DNA.
What risks would women (who are rarely
mentioned in discussions about human gene editing for
reproduction) be subject to as the ones who would carry
pregnancies started with genetically modified embryos
and deliver the resulting children (for themselves or for
others)? How could potential parents make informed
decisions when there would be unknown health risks
that might emerge during pregnancy for the woman and
the fetus, epigenetic effects, and health issues that might
not develop until adulthood or old age (or even in future
generations)? It would be extremely difficult, if not
impossible, to ethically conduct the kind of follow-up
studies that would be necessary to say that human
genome editing is safe enough to use in reproduction.
But focusing on these obvious safety risks takes too
narrow a view and overlooks the many serious social
and ethical risks that germline editing would pose.
Imagine wealthy parents being able to purchase
enhancements (real or perceived) for their children, and
the kind of world that would result if children’s
education and life chances were thought to be
determined at birth by their DNA. Imagine the long-
term consequences of imposing the preferences and
biases we hold today on the genes of all future
generations. Consider the potential effects on groups
that have less power in society and are already
discriminated against, including people with
disabilities, people of color, and women.
Ableism, racism, and reproductive injustices would
likely be exacerbated by human genome modification,
if it were ever allowed. These and other social
inequalities that already shape our lives could rapidly
grow worse, and new forms of inequality could be
introduced, leading to a new form of eugenics.
While it might seem possible to avoid such dire
outcomes by limiting the use of germline gene editing
to the prevention of serious diseases, this would be
extremely difficult. The line between therapy and
enhancement is fuzzy and would be nearly impossible
to enforce. How would we determine which diseases
are serious enough to edit out? And who would decide?
There are many disabled people who value their
differences as a form of human diversity and do not
think they need to be “treated” or “cured.” Allowing
just some uses of germline gene editing for
reproduction would mean opening the door to all uses.
For these reasons, over 40 countries have banned
human germline modification.
 CONCLUSION
New forms of human enhancement are increasingly
coming to play due to technological development. If
phenotypic and somatic interventions for human
enhancement pose already significant ethical and
societal challenges, germline heritable genetic
intervention, require much broader and complex
considerations at the level of the individual, society and
human species as a whole.
Germline interventions associated with modern
technologies are capable of much more rapid, large-
scale impacts and seem capable of radically altering the
balance of humans with the environment. We know
now that beside the role genes play on biological
evolution and development, genetic interventions can
induce multiple effects (pleiotropy) and complex
epigenetics interactions among genotype, phenotype
and ecology of a certain environment.
As a result of the rapidity and scale with which such
impact could be realized, it is essential for ethical and
societal debates, as well as underlying scientific studies,
to consider the unit of impact not only to the human
body but also to human populations and their natural
environment (systems biology). An important
practicable distinction between ‘therapy’ and
‘enhancement’ may need to be drawn and effectively
implemented in future regulations, although a distinct
line between the two may be difficult to draw.
In the future if we do choose to genetically enhance
human traits to levels unlikely to be achieved by human
evolution, it would be crucial to consider if and how our
understanding of humans and other organisms,
including domesticated ones, enable us to better
understand the implications of genetic interventions. In
particular, effective regulation of genetic engineering
may need to be based on a deep knowledge of the exact
links between phenotype and genotype, as well the
interaction of the human species with the environment
and vice versa.
For a broader and consistent debate, it will be essential
for technological, philosophical, ethical and policy
discussions on human enhancement to consider the
empirical evidence provided by evolutionary biology,
developmental biology and other disciplines.