Religions and mythologies around the globe describe creatures formed from the elements of two separate animals like griffons, sphinxes, and manticores (half-snake-half-lion). These animal blends are termed chimeras, and have always been the stuff of fiction… until recently. Within the past 25 years, several Cornell professors have worked with these once-fabled creatures in their laboratories, and some continue to work with modern-day chimeras in various forms. Although half-lion-half-eagle species are still considered a myth, scientists have managed to create goat-sheep, quail-chicken, and even mice-horse chimeras.

Unlike hybrids, which are a crossbreeding of two different species, chimeras retain identical cells from each species. In the case of goat-sheep chimeras, half of their cells are identical to goat cells and half of them are identical to sheep cells. This results in the individual physically being a medley of goat and sheep parts, growing a patchwork of sheep’s wool and goat hair.

A Hard Seed to Plant

Although scientists first created goat-sheep chimeras over 25 years ago, their success rate was extremely low. The immune system of most recipient animals rejected the implanted embryo, and successful pregnancies were rare.

Researchers believed that the fetus cells that become the placenta, which is in contact with the mother’s uterus, had to be similar enough in composition to the mother, or else her body’s immune system would launch an attack against the fetus.

“It was asked if the placenta could possibly be a mixed chimeric,” explained Prof. W. B. Currie, animal science. Currie’s research assisted in overcoming this problem. “The work was done at U.C. Davis but I shared in part of that research because I purified and then developed a species specific radioimmunoassay,” he said.

The placenta that formed from implanted chimeric fetuses was examined and a hormone specific to goats called placental lactogen, was spotted in a recipient sheep’s fetus, confirming that a pregnancy could survive if the placenta was a mix of goat and sheep cells.

Because chimera cells are either all goat or all sheep, breeding them results in either a pure goat or a pure sheep. If the sex cells, or gametes, in the chimera are those of a sheep, then only sheep genes are passed to the offspring.

Goat-Sheep ChimeraChimeras in Research

Prof. Drew Noden, biomedical science, works with a different type of chimera. He creates quail-chicken mixes in order to study how various tissues in the body form. By inserting quail cells into a chicken egg, the quail cells act as markers. The cells are easily identified when they differentiate and form the chick. By comparing the final product with where the cells were originally implanted, he and his team are able to track how each muscle develops, and where that tissue originated.

“Inside the embryo, many of the cells look alike and when they are moving in different directions, we would like to know for every tissue in the body where it came from in the embryo. And it is very important to understand where it came from because cells are making decisions throughout their lives and throughout their progeny’s lives,” explained Noden. “These decisions are very much affected by where they live. So if we don’t know what neighborhood every cell has lived in, we can’t begin to know what leads it to differentiate as a bone cell, or a cartilage cell.

“So this gave us the opportunity to create a chimera, where you transplant quail cells at the very early stages and put them into a chicken. No matter where those cells go if you take the tissue and you suction it and we look for a marker, and if any of those transplanted quail cells went there, you’ll find them.”

Cells scraped from its beak, for example, could be identical to quail cells while its wings and body would be of those of a chicken, if the transplanted cells were from a quail’s head. However, researchers seldom allow the embryos to hatch. Most fertilized eggs are terminated after the tissues have finished relocating, but before the chick has grown to the point of hatching.

Most chimeric animals are from species which are very closely related. Prof. Maria Flaminio, clinical sciences, currently works on creating horse-mice chimeras. She plans to insert into transgenic mice a horse gene which codes for the production of B and T lymphocytes (white blood cells). Transgenic animals have a gene intentionally altered so that the gene is either suppressed or exaggerated. For her experiments the mice she purchases have been altered so that their immune system is partly defective and they don t produce B and T cells, which are active in immune response.

“Because they don t have these cells, we can potentially graft or transplant these immune cells from other species,” she explained. “Hopefully these cells will populate their immune system and will become the effector cells — the cells that will generate the immune response. The reason we need the mouse is because the horse has a natural disease that manifests late in age.”

Human Sheep Chimeras

The first human-sheep chimera was created in March of last year by Prof. Esmail Zanjani, University of Nevada. This animal contains 15 percent human genes and has the body of a sheep but with organs that are partly-human. A major goal of this research is to create a sheep with partly human liver, lungs, heart, and brain. A medical professional can then harvest these organs for transplantation into a human recipient.

This form of chimerism is considered controversial from an ethical standpoint and because of the threat of silent viruses — viruses that exist harmlessly in animals but when transferred to humans, can become destructive. One of the most notable of these silent viruses is believed to be HIV. It is now believed that HIV was a mutation of SIV, a virus which existed harmlessly in other primates like the white-collared monkey.