The Chimera was a hybrid monster in Greek mythology,
It was the sibling of the three headed
dog, Cerberus and the Lernaean Hydra, a serpentine creature with multiple
heads. The Chimera had the head and body
of a lion, as well as the head of a goat that was attached to its back, and a
tail that ended on a head of a snake.
The Chimera
Scientifically, Chimeras are organisms with two sets
of DNAs which can produce two different
organisms. Among humans, they are
seen in two situations. In the first one, they may be seen in twin pregnancies
– one twin may die in very early pregnancy and the other twin may absorb the
dead twin. This twin can then have two sets of DNA – one its own plus the set
from its twin.
Human chimeras can also occur after bone marrow
transplantations. Bone marrow from a healthy donor replaces the damaged marrow of the recipient. The new
marrow will continue to produce new blood cells
and the person may then have one set of DNA in the blood cells and
another in the other tissues.
Pregnant women may also have DNAs from fetal cells
circulating in their blood as well as miniscule amounts deposited in their
organs. This is called microchimerism and does not produce any noticeable
symptoms in the mother.
Chimeras of mouse-rat combinations have been created
earlier in the lab. But the present experiment of a human-pig embryo
was carried out to identify the
potential of using larger animals since human organs of the appropriate size can only develop
in animals with similar sized organs.
This could help ease the shortage of human donors for transplants.
Organs like the heart, liver and pancreas can be
grown in pigs in place of their own. The animals would be euthanized before the
organs are harvested for human transplantation. Since the organs would be made
of mainly human cells, the risks of rejecting the transplant would be greatly
minimized.
This is the first time that genetic material from
two large species have been combined in a single individual embryo. It is an important step towards growing
generating human hearts, kidneys and livers in an animal for transplantation.
The process
begins with pluripotent cells – cells capable of developing into any
tissues system and organs.
Human pluripotent cells were collected from the
foreskin and labelled with fluorescent markers. About 3-10 of these cells were
then inserted into the inner cell mass of a developing pig embryo. About 2000
of these hybrid embryos were implanted into sows and 150 developed into
human-pig chimeras. An artificially inseminated sow was implanted with 17
normal embryos as controls.
PHOTOGRAPH COURTESY JUAN CARLOS IZPISUA BELMONTE
The chimeras were harvested at 28 days which is the
duration of the first trimester of a pig. Immunohistochemistry confirmed the fluorescent signal and identified the human cells. There
were only about 1 human cell in 1000 pig cells. But these cells could generate
the precursors of the muscle, heart, liver, pancreas and spinal cord tissue.
Juan Carlos Izpisua Belmonte, who led the work on the part-pig, part-human embryos at the Salk Institute for Biological Studies in La Jolla, California, said: “The ultimate goal is to grow functional and transplantable tissue or organs, but we are far away from that. This is an important first step.” Even before that is achieved, he said, putting human cells in animals could pay off for studies of how genetic diseases develop and for screening potential drugs.
Juan Carlos Izpisua Belmonte, who led the work on the part-pig, part-human embryos at the Salk Institute for Biological Studies in La Jolla, California, said: “The ultimate goal is to grow functional and transplantable tissue or organs, but we are far away from that. This is an important first step.” Even before that is achieved, he said, putting human cells in animals could pay off for studies of how genetic diseases develop and for screening potential drugs.
ETHICAL CONCERNS
The study has
raised ethical concerns. Nightmarish scenarios of animals with intelligent
human brains are being discussed. The potential of bizarre humanised animals
roaming in the wild have been raised.
Other questions have also come up – what happens if the human cells
populate the pig brain and the chimera has a human thought? Or what if the
human cells cannibalise the pig cells and what we get is a more human and less
pig chimera rather than a pig with human organs. Human genes in the pig sperm or ovum can result in these
genes being passed on to the pig offspring.
These ethical concerns have caused governments to
deny funding to these experiments. The present experiment was supported by
private sponsorship.
Izpisua Belmonte has said that these experiments are
meticulously conducted in laboratories under tightly controlled methods. But he
has acknowledged that the idea of having an animal being born composing of
human cells creates some feelings that need to be addressed. This will need to
be prevented by genetic engineering – switching off genes so that only human
cells develop into the target organs like liver and heart . Genetic engineering
can also ensure that no human cells reach the brain of the pig embryo or form
any part of the sperms or eggs.
The human-pig chimera project is an important first step towards the goal of developing viable and physiologically
active human organs in animals. Further
improvements in gene manipulation technologies should help to overcome shortfalls in human organs
for transplantation.
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