Transgenic humans .

Topics
1. Introduction.
2. History.
3. Types.
4. Transgenic plants
5. Transgenic animals
6. Methods
7. Transgenic human
8. Does this mean we are getting the designer babies?
9. Critics
10. Difference b/w GMO and transgenic?
 1. INTRODUCTION
Transgene
A transgene is an exogenous gene that has been introduced into the genome of
another organism, and a transgenic species is one whose genome has been genetically altered.

Transgenic organisms
Transgenic organism is defined as the living organisms containing
genetic material into which DNA from a different organism has been artificially introduced.

2. History:
The first GMO was created in 1973 by Stanley N. Cohen and Herbert Boyer,
demonstrating the creation of a functional organism that combined and replicated genetic
information from different species. In mid-1974, very soon after the first GMO was created,
scientists called for and observed a voluntary moratorium on certain recombinant DNA
experiments. One goal of the moratorium was to provide time for a conference that would
evaluate the state of the new technology and the risks, if any, associated with it.That
conference concluded that recombinant DNA research should proceed but under strict
guidelines. Such guidelines were subsequently promulgated by the National Institutes of
Health in the United States and by comparable bodies in other countries. These guidelines
form the basis upon which GMOs are regulated to this day.

3. Types:
There are three types of trasgenesis.
1. Transgenic plants.
2. Transgenic animals.

Transgenic plants
Transgenic plants are plants that have been genetically engineered, a
breeding approach that uses recombinant DNA techniques to create plants with new
characteristics.

History
The first plant produced in that way came in 1982, an antibiotic-resistant tobacco plant. The
first field trials occurred in France and the USA in 1986, using tobacco plants engineered
for herbicide resistance. In 1987, Plant Genetic Systems (Ghent, Belgium), founded by Marc
Van Montagu and Jeff Schell, was the first company to genetically engineer insect-resistant
(tobacco) plants by incorporating genes that produced insecticidal proteins from Bacillus
thuringiensis (Bt).
The People's Republic of China was the first country to allow commercialized transgenic
plants, introducing a virus-resistant tobacco in 1992,which was withdrawn in 1997.In 1995,
Bt Potato was approved by the US Environmental Protection Agency, making it the country's
 first-pesticide producing crop. In 1995 canola with modified oil composition (Calgene), Bt
maize (Ciba-Geigy), bromoxynil-tolerant cotton (Calgene), Bt
cotton (Monsanto), glyphosate-tolerant soybeans (Monsanto), virus-tolerant squash
(Asgrow), and additional delayed ripening tomatoes (DNAP, Zeneca/Peto and Monsanto)
were approved.As of mid-1996, 35 approvals had been granted to commercially grow 8
transgenic crops and one flower crop (carnation), with 8 different traits in 6 countries plus the
EU.

Applications

Some of the important ones are listed:

i. Resistance to biotic stresses i.e. resistance to diseases caused by insects, viruses, fungi and
bacteria.

ii. Resistance to abiotic stresses-herbicides, temperature (heat, chilling, freezing), drought,

salinity, ozone, intense light.

iii. Improvement of crop yield, and quality e.g. storage, longer shelf life of fruits and flowers.

iv. Transgenic plants with improved nutrition.

v. Transgenic plants as bioreactors for the manufacture of commercial products e.g. proteins,
vaccines, and biodegradable plastics.

Advantages
1. Improvement in Yield
2. Improvement in Insect and Disease Resistance
3. Improvement in Quality
4. Herbicide Resistance
5. Resistance to Abiotic Stresses
6. Industrial Products
7. Rapid and Accurate Technique
8. No Barrier for Gene Transfer
 Production of transgenic plants by use of co-integrated Ti plasmids

Transgenic animals
A transgenic animal is one whose genome has been altered by the
transfer of a gene or genes from another species or breed.

History
The first successful transfer of embryos was achieved by Walter Heape in Angora
rabbits in 1891. Another important component is the ability to manipulate the embryo. In
vitro manipulation of embryos in mice was first reported in the 1940s using a culture system.
This was made possible through the efforts of Ralph Brinster, attached to the University of
Pennsylvania, who in 1963 devised a reliable system to culture eggs, and that of Teh Ping
Lin, based at the California School of Medicine, who in 1966 outlined a technique to micro-
inject fertilised mouse eggs which enabled the accurate insertion of foreign DNA.

The first genetic modification of animals was reported in 1974 by the virologist Rudolph
Jaenisch, then at the Salk Institute, and the mouse embryologist Beatrice Mintz at Fox Chase
Cancer Center. They demonstrated the feasibility of modifying genes in mice by injecting the
SV40 virus into early-stage mouse embryos. The resulting mice carried the modified gene in
all their tissues. In 1976, Jaenisch reported that the Moloney Murine Leukemia Virus could
also be passed on to offspring by infecting an embryo. Four years later, in 1980, Jon Gordon
and George Scango together with Frank Ruddle, announced the birth of a mouse born with
genetic material they had inserted into newly fertilised mouse eggs. By 1981 other scientists
had reported the successful implantation of foreign DNA into mice, thereby altering the
genetic makeup of the animals. This included Mintz with Tim Stewart and Erwin Wagner at
the Fox Chase Cancer Center in Philadelphia; Brinster and Richard Palmiter at the University
of Washington, Seattle; and Frank Costantini and Elizabeth Lacy at Oxford University.

Methods
There are three principle methods used for the creation of transgenic animals.
1. DNA microinjection.
2. Embryonic stem cell-mediated gene transfer
3. Retrovirus-mediated gene transfer (RMGT).

1. DNA microinjection:
This method involves the direct microinjection of a chosen gene construct (a single gene or a
combination of genes) from another member of the same species or from a different species,
into the pronucleus of a fertilized ovum. It is one of the first methods that proved to be
effective in mammals (Gordon and Ruddle, 1981). The introduced DNA may lead to the
over- or under-expression of certain genes or to the expression of genes entirely new to the
animal species. The insertion of DNA is, however, a random process, and there is a high
probability that the introduced gene will not insert itself into a site on the host DNA that will
permit its expression. The manipulated fertilized ovum is transferred into the oviduct of a
recipient female, or foster mother that has been induced to act as a recipient by mating with a
vasectomized male.
A major advantage of this method is its applicability to a wide variety of species.

2. Embryonic stem cell-mediated gene transfer.

This method involves prior insertion of the desired DNA sequence by homologous
recombination into an in vitro culture of embryonic stem (ES) cells. Stem cells are
undifferentiated cells that have the potential to differentiate into any type of cell (somatic and
germ cells) and therefore to give rise to a complete organism. These cells are then
incorporated into an embryo at the blastocyst stage of development. The result is a chimeric
animal. ES cell-mediated gene transfer is the method of choice for gene inactivation, the so-
called knock-out method.
This technique is of particular importance for the study of the genetic control of
developmental processes. This technique works particularly well in mice. It has the advantage
of allowing precise targeting of defined mutations in the gene via homologous recombination.
 Retrovirus-mediated gene transfer.
To increase the probability of expression, gene transfer is mediated by means of a carrier or
vector, generally a virus or a plasmid. Retroviruses are commonly used as vectors to transfer
genetic material into the cell, taking advantage of their ability to infect host cells in this way.
Offspring derived from this method are chimeric, i.e., not all cells carry the retrovirus.
Transmission of the transgene is possible only if the retrovirus integrates into some of the
germ cells.
For any of these techniques the success rate in terms of live birth of animals containing the
transgene is extremely low. Providing that the genetic manipulation does not lead to abortion,
the result is a first generation (F1) of animals that need to be tested for the expression of the
transgene. Depending on the technique used, the F1 generation may result in chimeras. When
the transgene has integrated into the germ cells, the so-called germ line chimeras are then
inbred for 10 to 20 generations until homozygous transgenic animals are obtained and the
transgene is present in every cell. At this stage embryos carrying the transgene can be frozen
and stored for subsequent implantation.

Example:
The first transgenic animals were mice created by Rudolf Jaenisch in 1974. Jaenish
successfully managed to insert foreign DNA into the early-stage mouse embryos; the
resulting mice carried the modified gene in all their tissues. Subsequent experiments,
injecting leukemia genes to early mouse embryos using a retrovirus vector, proved the genes
integrated not only to the mice themselves, but also to their progeny.

Transgenic human
There is no work yet have been done on this in humans. Because it needs much precision.
Scientists are only able to produce the designer babies by GMO technique which is quite
different from transgenic.
The first known attempt at creating genetically modified human
embryos in the United States has been carried out by a team of researchers in Portland,
Oregon, MIT Technology Review has learned.
The effort, led by Shoukhrat Mitalipov of Oregon Health and Science University, involved
changing the DNA of a large number of one-cell embryos with the gene-editing technique
CRISPR (Clustered Regularly Interpeaced Short Palandromic Techniques), according to
people familiar with the scientific results.
In altering the DNA code of human embryos, the objective of scientists is to show that they
can eradicate or correct genes that cause inherited disease, like the blood condition beta-
thalassemia. The process is termed “germ line” because any genetically modified child would
then pass the changes on to subsequent generations via their own germ cells—the egg and
sperm.
Elsewhere in the Boston area, scientists are exploring a different approach to engineering the
germ line, one that is technically more demanding but probably more powerful. This strategy
combines CRISPR with unfolding discoveries related to stem cells. Scientists at several
centers, including Church’s, think they will soon be able to use stem cells to produce eggs
and sperm in the laboratory. Unlike embryos, stem cells can be grown and multiplied. Thus
they could offer a vastly improved way to create edited offspring with CRISPR. The recipe
goes like this: First, edit the genes of the stem cells. Second, turn them into an egg or sperm.
Third, produce an offspring.

“The human genome is not perfect. It’s ethically imperative to

positively support this technology.”
Scientists thought that this could help us in different ways.

Experiments are being done on the genetically modified humans, but till now there are
different ethical problems. Many countries didn’t allow this.
In a U.S. first, a team of biologists has edited a human embryo’s DNA. The technique has
been used before by scientists in China, but never in the United States, where
the ethical debate over editing embryos rages on with no consensus in sight. And according to
the U.S. team, their trial has achieved an unprecedented level of success.

Does this mean we're getting designer babies?

Though there’s been concern that people would use CRISPR to make so-called
designer babies, the most useful genes to edit would be those for serious genetic diseases.
Some of these are so serious that the baby either cannot survive to term or will die shortly
after birth. Others are debilitating, chronic conditions. The ability to change a mutation and
prevent a baby from such suffering would be invaluable to some parents, even though the
idea might make others uneasy. There's also concern that because CRISPR effectively edits
every cell in a future baby, including sex cells, that it involves what's called "germline
editing." It's not just changing one child's genes, but also changing everyone in that child's
future lineage. Do you have the right to change a whole branch of a family tree? And if
there's some downside scientists can't predict—something that could be passed down to
offspring and their offspring—is it ethical to put that out into the gene pool?
The degree to which we should be allowed to edit a human being is another moral quagmire.
The National Academies of Science and Medicine have already said that CRISPR editing
shouldn't be used for enhancements like super-intelligence (even if we knew how to do that in
the first place, which we do not), and that it should be reserved for serious diseases or
disabilities.
In china, a Chinese group from Sun Yat-sen University, reported that they had, in fact, done
it: they had created the first genetically-modified human embryo.

Critics:
Some critics say germline experiments could open the floodgates to a brave new world of
“designer babies” engineered with genetic enhancements—a prospect bitterly opposed by a
range of religious organizations, civil society groups, and biotech companies.
Critics warn that allowing embryos to be edited opens the door to designer babies and
genetically modified humans.
Anne Scanlan of the charity LIFE said: “The HFEA now has the reputation of being the first
regulator in the world to approve this uncertain and dangerous technology. It has ignored the
warnings of over a hundred scientists worldwide and given permission for a procedure which
could have damaging far-reaching implications for human beings."
In china, in February of 2017 a panel met to discuss the ethics behind gene editing in human
embryos. The panel agreed that - with heavy safeguards and only in the case of deadly
disease, they MIGHT very cautiously CONSIDER allowing for gene editing in human
embryos. In fact, the language was even more judicious than that. The panel agreed that a
clinical trial might be approved, “but only following much more research” and “only for
compelling reasons and under strict oversight.

Our shared humanity is the starting point for every struggle for
equality. Germline gene editing is prohibited by international
human rights treaties and more than forty countries.
Difference b/w GMO and transgenic?
The two terms “transgenic organism” and “genetically modified organism” are commonly
used interchangeably, but that is not always correct. While all transgenic organisms are
GMOs, not all GMOs are transgenic.
What Makes an Organism Transgenic?
We will start with transgenic organisms, the are species that have been modified by bringing
in the DNA of a species different than the one being altered.

A great example of this can be seen in the ever so popular aquarium fish, the GloFish.
Basically, a biologist saw a fish and they saw a glowing jellyfish and they thought,
GLOWING FISH. They identified the gene that caused these jellyfish to light up like a
Christmas tree and then inserted that gene into the DNA of the zebra fish and then…..a
glowing fish was created. Essentially, this technology gives organisms a function they did not
previously have by copying it from another organism. So, let’s get this straight. Transgenic
organisms are all GMOs because they have been modified at the genomic level by using
DNA from a different organism (like the GloFish), but not all GMOs are transgenic.

A more specifically defined type of GMO is a "transgenic organism." This is an organism

whose genetic makeup has been altered by the addition of genetic material from an unrelated
organism. This should not be confused with the more general way in which "GMO" is used to
classify genetically altered organisms, as typically GMOs are organisms whose genetic
makeup has been altered without the addition of genetic material from an unrelated organism.
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