Evolution of the Human Chimera

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.

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.