In 1862, Mary Jane Merrick was at a fair when she was knocked over by an elephant. Some months later, she gave birth to an apparently healthy boy named Joseph. However, within a few years, Joseph had developed thick skin lesions on his face. As he grew, the lesions worsened and spread and skeletal abnormalities began to manifest, particularly affecting his skull. By his teens, his appearance was so disturbing that he was having trouble finding work.
After his mother’s death, Joseph was mistreated by his father and step-mother. He left home and lived in poverty until, in desperation, he approached a showman to offer himself as an exhibit. Given the epithet The Elephant Man, he became a popular attraction. He later resided at the London Hospital where he became well-known among London’s upper class.
The weight of Merrick’s head meant that he was unable to lie down without risking a broken neck. He would sleep in a sitting position. On April 11, 1890, at the age of twenty-seven, he was found lying on his bed, dead of a dislocated neck. His doctor and friend, Frederick Treeves, believed that he attempted to sleep lying down out of a need to normalise his behaviour.
Until his death, Joseph Merrick held the belief that his mother’s elephant accident elephant was the cause of his condition. Most likely, it was a case of Proteus syndrome, a rare genetic disorder named after the shape-shifting Greek god of the sea. A 2011 study published in the New England Journal of Medicine resolves the question of the gene involved.
Biopsies were taken from affected and unaffected tissues from twenty-nine Proteus syndrome patients. Sequencing of exomes (DNA that codes for a protein product, constituting about 1% of the human genome) showed that, in affected tissues, a gene called AKT1 was mutated. AKT1 is involved in the growth and death of cells. The mutation was uncommon in unaffected tissue.
The study demonstrated that Proteus syndrome is a mosaic disorder, one caused by a mutation that occurs during prenatal development. The mutation is then propagated only through cells that are descended from the original mutated cell, resulting in incomplete distribution of the abnormality throughout the body. Germline mutations of AKT1 cause embryonic death.
Similar to mosaicism, chimerism occurs when two separately fertilised ova fuse into a single zygote.; essentially, two (non-identical) twins fuse into a single individual in utero. The result is a person carrying the genomes of two people in different parts of their bodies. Usually, the condition has little or no consequence. However, with the advent of genetic testing, chimerism may cause complications. This was most dramatically demonstrated by the ordeal suffered by Lydia Fairchild.
While pregnant, Lydia and her recently estranged husband submitted to genetic testing as part of Lydia’s application for child support. Her husband was found to be the father but Lydia’s DNA did not match. She was accused of fraud and her children were taken into care.
At the time, Lydia was pregnant with her third child. At the birth, a court-appointed witness was present to take samples from both the baby and Lydia. The tests on these returned the same result – the child the witness had seen Lydia give birth to was genetically not her child.
Testing of a cervical smear finally clarified the situation – Lydia was a chimera.