Most of the time, animals develop from single zygotes; a human develops from one fertilized egg. Genetic chimerism or a chimera is an organism that develops from at least four parent cells. This can occur in a variety of ways, from two fertilized eggs, for instance, or two embryos fusing. The exact effect chimerism has on a person also varies. Due to the rarity of the condition and restrictions on human-based studies, the medical community is still seeking information about human chimerism.

Rate of Occurrence

Medical experts cannot predict how many human chimeras exist in the world. Not only is the condition incredibly rare, but obvious signs and symptoms may never develop. It is possible for a person with chimerism never to realize their genetic difference. Modern medical literature records only around 100 cases of human chimerism. A study from the late 1990s states fertility treatments such as in vitro fertilization may increase the likelihood of a child being born with chimerism. However, there is not enough research into this topic to verify the accuracy of these claims.

Microchimerism

If a person’s genetics contain a small number of cells from another individual, this is microchimerism. These cells are genetically distinct from the cells of the host. Fetomaternal microchimerism is the most common form in humans. A fetus’ cells travel through the placenta and into the mother. The pregnant mother then absorbs them. These cells can survive in the mother’s body for several decades. Microchimerism can also occur during gestation of twins in the womb. The twins may share cells with each other or their mother.

Artificial Chimerism

Some studies and researchers use the term artificial chimerism to describe chimerism that occurs as a result of blood, stem cell, or bone marrow transfusion. This form of chimerism is uncommon due to the modern practice of treating blood with radiation. This helps the transplant recipient better absorb the cells in the blood and reduces the likelihood of the foreign cells permanently existing in the new host. Due to the infrequency of this form of chimerism, most medical experts consider it a subtype of microchimerism.

Effects of Microchimerism

The potential health effects of microchimerism are still unknown. Some researchers suggest that the foreign fetal cells could trigger a reaction similar to that of a host rejecting a transplant, eventually leading to an autoimmune disease. Other researchers suggest the fetal cells travel to areas of damaged or diseased tissue and act as stem cells, repairing the damaged areas. There may also be a link between microchimerism and breast cancer; physicians sometimes discover fetal immune cells in breast cancer stroma. However, the cells could be the cause of cancer, or they could be trying to prevent it, as per the previous theory. Again, there is not enough research on the matter to know for sure.

Tetragametic Chimerism

One of the more complex forms of chimerism is tetragametic chimerism — two separate sperm fertilize two separate ova. During the blastocyst or zygote stage, the cells then merge and fuse together. The resulting organism is a chimera — a fusion of two non-identical twins. Due to this, the person with chimerism may be male, female, or possess intersex characteristics. It is also possible for this to occur in the case of potential identical twins, but the person’s separate genetics would be too similar for them to qualify as a chimera.

Visual Effects of Tetragametic Chimerism

Despite the unique qualities of the cells, chimerism does not always produce noticeable effects. Some physical changes are too subtle to suggest any underlying cause, much less differing genetics. For example, a person may have one straight and one hitchhiker’s thumb or have slightly different hair growth rates on different areas of the body. Chimerism is also one of the causes of heterochromia, or eyes of different colors. If the fused cells were zygotes of different sexes, the resulting individual may have ambiguous or intersex genitalia. If the fused cells were blastocysts of different sexes, it is possible for genitals of both sexes to form, either ovary and testis, or ovotestes.

Other Effects of Tetragametic Chimerism

As a person with chimerism develops, his or her body may undergo unique changes. For example, her liver may consist of cells with one set of chromosomes, while her kidney carries an entirely different set. Some individuals with chimerism develop distinctive Blaschko’s lines under the skin. These lines are generally invisible but become visible under a certain spectrum of UV light. In some people with chimerism, these lines form an arrow that points downwards from the shoulders.

Notable Occurrences

There have been several humans with chimerism in the spotlight in recent history.

• In 1953, physicians discovered a woman with two different blood types. This was due to the presence of her twin brother’s cells in her body.
• In 1998, a male human conceived through in vitro fertilization was born with partially developed female organs.
• In 2002, a woman named Lydia Fairchild did not receive public assistance because a DNA test showed she was not related to her children. A lawyer, who possessed cursory knowledge of chimerism, suggested that Lydia could be one such case, and additional tests proved his theory correct.

Diagnosis

Physicians rarely test people for chimerism, but if they have a reason to suspect the condition, they will perform genetic testing. These processes show whether a person’s blood cells contain DNA that is not present in another part of their body. In some cases, it is possible for a physician to uncover chimerism during blood tests because the patient has multiple blood types. Routine tests before an operation such as an organ transplant may also discover foreign cells.

Ethics and Legislation

Many researchers wish to discover more about chimerism, but ethical and legislative complications prevent the studies. Human trials fall under strict regulations and guidelines. Additionally, the unknown risks of experimenting with chimerism pose a danger to human subjects. However, using an animal subject is also controversial. Some individuals believe genetic mixing and altering is ethically wrong. Several countries have laws that ban or heavily restrict these studies using human cells. The U.S. Senator Samuel Brownback introduced The Human Chimera Prohibition Act in 2005. The bill failed to make it into law and there has not been any further attempt to regulate chimera research in the United States.