An animal chimera is a single organism composed of cells from at least two genetically distinct individuals, meaning it has two separate sets of DNA. The term originates from the Greek mythological creature, reflecting the composite nature of these biological entities. Chimeras are distinct from mosaics, which have genetically different cells from a single zygote, and hybrids, which result from cross-breeding species. In a chimera, separate cell populations from different zygotes co-exist, sometimes resulting in traits like two different eye colors.
Methods of Creating Animal Chimeras
One primary method is embryo aggregation, where cells from two or more different embryos are physically combined. This is performed at an early developmental stage when embryonic cells are adaptable and can integrate to form a cohesive whole. The resulting animal will have a mixture of cells from each contributed embryo distributed throughout its body.
Another technique is blastocyst injection, which involves injecting pluripotent stem cells into a host blastocyst. Pluripotent stem cells can develop into any cell type in the body. These injected cells integrate into the inner cell mass of the host blastocyst, contributing to the development of all tissues and creating a chimera.
Scientists may use embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), which are generated by reprogramming adult cells back into a stem-cell-like state. The use of iPSCs allows for the creation of chimeras with cells of a specific genetic makeup. This is useful for studying certain diseases or developmental processes.
To enhance precision, researchers employ gene-editing technologies like CRISPR-Cas9 to create a developmental “niche” within the host embryo. For example, by inactivating a gene necessary for a specific organ’s development in the host, a void is created. When pluripotent stem cells from a donor are injected, they can preferentially fill this empty niche, forming a chimera with an organ derived almost entirely from the donor cells.
Naturally Occurring Animal Chimeras
Chimerism also occurs naturally in the animal kingdom. These instances provide valuable insights into developmental biology and reveal the flexibility of biological systems in accommodating foreign cells.
One example is freemartinism in cattle. When a female calf is a twin to a male, they often share a placental blood supply, allowing for the exchange of cells and hormones. As a result, the female calf becomes a chimera, incorporating male cells into her body, which leads to infertility and the development of some male characteristics.
Microchimerism is a more subtle form involving a small number of cells from another individual. During pregnancy, fetal cells can cross the placenta and reside in the mother’s body for years. Maternal cells can also be transferred to the fetus, meaning many individuals carry a small population of their mother’s cells.
An extreme case is found in some deep-sea anglerfish. When a tiny male finds a larger female, he bites and physically fuses into her body. Their circulatory systems merge, and the male becomes permanently attached, losing his organs except for his testes, which turns the female into a chimera carrying a living sperm bank.
Research Applications of Animal Chimeras
One application of chimeras is in studying early embryonic development. By labeling cells from one embryo with a fluorescent marker before combining them, researchers can track the fate of the labeled cells. This allows them to map how cells migrate and specialize to form complex tissues and organs, building our understanding of how a fertilized egg develops.
Chimeras are also invaluable for modeling human diseases and testing drugs. Scientists can create animals with specific human tissues, such as a mouse with a humanized liver to study hepatitis. These chimeric models allow for studying disease progression and testing new drugs in a more biologically relevant context, which could accelerate the development of new treatments.
Perhaps the most ambitious application is in organogenesis, the effort to grow human organs in animal hosts for transplantation. The concept involves creating a genetic “niche” in an animal embryo, such as by deleting a gene for pancreas development in a pig. Human pluripotent stem cells are then injected, with the hope they will colonize the niche and develop into a functional human organ to address organ shortages.
Ethical Considerations and Governance
The creation of animal chimeras, particularly those with human cells, raises complex ethical questions. These concerns range from the welfare of the animals to the boundaries between species and the moral status of these organisms. As the science advances, it is important to have robust ethical frameworks and governance structures to guide research responsibly.
A primary concern is animal welfare. The procedures to create chimeras can be invasive, and the resulting animals could suffer from unforeseen health problems. Researchers have a responsibility to ensure these animals are treated humanely, minimize potential suffering, and establish clear ethical endpoints for experiments.
More complex concerns arise when human cells are introduced into animals. The most sensitive areas involve the potential for human cells to contribute to an animal’s brain or its germline (sperm and eggs). There are concerns that introducing human neural cells could lead to cognitive changes, while the possibility of an animal producing human gametes creates unease about human reproductive material in a non-human host.
These possibilities touch on views about species boundaries, sometimes causing a visceral public unease. In response, regulatory bodies have established guidelines to oversee this research. For example, the National Institutes of Health (NIH) restricts funding for certain experiments, and the International Society for Stem Cell Research (ISSCR) provides a framework for conducting research responsibly, often prohibiting the breeding of animals that may have human germ cells.