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Monday, July 08, 2013

Mouse with human ear

Back in 1997, a rather bizarre photograph suddenly became very famous. It showed a totally hairless mouse, with what appeared to be a human ear growing out of its back. That photograph prompted a wave of protest against genetic engineering, which continues today. But there was absolutely no genetic engineering involved in getting that ear to cover almost all of the mouse's back.

The layperson might ask, why would you want to have a "spare" human ear? The reason is that it's very difficult to repair the ear. The ear is mostly made of cartilage, which is tricky to work with, and at the same time, has a highly visible and complicated shape. So a spare ear would solve a lot of problems. The Indian surgeon, Sushruta, describes operations to repair the ear in 600 BC. The ear is often damaged in car accidents, fights or fires. There is also the disease called "microtia", which means literally "small ear". It can range from a slightly smaller ear, to almost complete absence of the external ear. It can occur in up to 1 in 1,000 births.
In August 1997, Joseph Vacanti and his colleagues wrote their ground-breaking paper in the journal, Plastic and Reconstructive Surgery. The publicity was enormous, helped by a film made by the BBC's Tomorrow's World.
On October 11, 1999, the anti-genetics group, Turning Point Project, placed a full-page ad in the New York Times showing the photo of the mouse with the human ear, with a misleading caption that read, "This is an actual photo of a genetically engineered mouse with a human ear on its back". In truth, the mouse was not genetically engineered, and the "ear" had no human cells in it.
A "genetically engineered mouse" would have to have its DNA (its genetic "blueprint") modified. The Turning Point propaganda implied that some DNA from a human (the section that has the blueprint for making the human ear) had been inserted into the DNA of the mouse. Then, this human DNA had somehow taken over the mouse DNA, and commanded it to grow a human ear. But it never happened - the mouse in the famous photo had never been genetically engineered.
The "mouse-ear" project began in 1989, when Charles Vacanti (brother of Joseph) managed to grow a small piece of human cartilage on a biodegradable scaffold. The scaffold was the same synthetic material (99% polyglycolic acid and 1% polylactic acid) used in dissolving surgical stitches. In the body, it degrades into carbon dioxide and water. The fibres of this material were woven into a loose mesh that was 97% air - leaving lots of room for cells to grow into. His surgeon colleagues had told him that the human ear was the body's most difficult cartilaginous tissue to reconstruct and rebuild - and that they would love to have a "spare" ear to transplant.
After 8 years, Charle's team got to the stage where they could mould their sterile biodegradable mesh into the exact shape of a 3 year-old's ear. The next step was to seed this ear-shaped scaffold with cartilage cells from the knee of a cow (remember how I said that the famous mouse-ear had absolutely no human cartilage cells in it). The team used a Nude Mouse. The Nude Mouse got its name thanks to a random mutation in the 1960s that left the mouse with no hair, and virtually no immune system. The lack of hair was irrelevant to their project, but the lack of immune system was critical. It meant that the mouse would not reject the foreign cow cartilage cells. The only purpose of the mouse in this project was to supply power to let the cow cartilage cells grow. The cartilaginous ear was implanted under the skin layer of the mouse, but over the muscle layer. Over some three months, the mouse grew extra blood vessels that nourished the cow cartilage cells, that then grew and infiltrated into the biodegradable scaffolding (which had the shape of a human ear). By the time that the scaffolding had dissolved away, the cartilage had enough structural integrity to support itself.
That cartilaginous structure that looked like a human ear was never transplanted onto a human, because it was full of cow cells and would have been rejected by a person's immune system.
But the same Tissue Technology was used for 12 year-old Sean G. McCormack, who was born with Poland's Syndrome. He had absolutely no bone or cartilage on his left chest. His heart and lungs were protected only by skin. This was a problem everyday, and especially in his beloved sport of baseball in which he was a star pitcher - because a single ball to the chest could kill him. The Vacanti brothers used McCormack's own cartilage cells to grow a "chest plate", the size of a CD, on their synthetic biodegradable polymer, that was moulded to the shape of his chest. They implanted the seeded cartilage in his chest, and it grew with him.
But like the mouse with the "human" ear, there was absolutely no genetic engineering involved - only genuine scientific invention…

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