The World's First Sciatic Nerve Transplant

Researcher name: 
Alan R. Hudson, MB, FRCSC & Susan E. Mackinnon, MD, FRCSC

The sciatic nerve is approximately the width of three lead pencils placed side-by-side and contain many thousands of axons. The axons convey messages from the spinal cord to the muscles and other axons convey messages in the opposite direction, taking information from the skin to the spinal cord. Thus, if the nerve is irreparably damaged, the muscles supplied by that nerve will not be able to work, and the area of the skin supplied by that nerve will be anaesthetic.

A human nerve is analogous to a telephone cable. The minute wires are called "axons" and are, in fact, the very long drawn-out processes of nerve cells situated in, or close to, the spinal cord. In the case of the sciatic nerve, the single cell processes stretch from the lower third of the spine all the way down to the tip of the great toe. The insulation around each of the little wires is provided by Schwann cells. Just as we see in a telephone cable, the axons, with their surrounding Schwann cells, are bundled together to form a nerve. The sciatic nerve is approximately the width of three lead pencils placed side-by-side and contain many thousands of axons. The axons convey messages from the spinal cord to the muscles and other axons convey messages in the opposite direction, taking information from the skin to the spinal cord. Thus, if the nerve is irreparably damaged, the muscles supplied by that nerve will not be able to work, and the area of the skin supplied by that nerve will be anaesthetic.

When a nerve is irreparably damaged, the injured segment has to be cut out and replaced by sewing in nerve grafts. Usually the surgeon harvests unimportant nerves in the legs and uses these grafts in the same patient to make up gaps in important nerves supplying the arms. Because this is the patient's own tissue, no rejection results.

In 1970, Dr. Hudson studied the way in which nerves regrew through autografts. These experiments were conducted in mice and rats, as we required living animals in which the regeneration process could be observed over weeks and months. Dr. Susan Mackinnon began working in the laboratory and specifically studied the use of transplanted nerve grafts from other animals of the same species. She had to establish testing methods so that the degree of rejection of the transplanted nerve graft could be measured, and she then conducted a series of experiments in which the rejection phenomenon was suppressed, so as to allow regrowth through the nerve grafts in a manner analogous to regrowth through autografts. Dr. Judy Wade, an expert immunologist, supervised a further series of experiments which were then repeated in primates. This step was necessary to finally establish the dosage of suppressive drugs that was required and also to establish that the patterns of regeneration and rejection seen in mice and rats was similar to that seen in monkeys, prior to the use of these techniques in humans. Over the years, Drs. Hudson, Mackinnon, and Wade were assisted by a large number of young men and women training in the Department of Surgery at the University of Toronto.

Finally, a submission was made to the Ethics Committee in which all the experimental work was presented and the risks and benefits of nerve transplants were presented. Permission was given to start a limited clinical trial.

Young Matthew Beech had had his sciatic nerve destroyed by the propeller of a boat while he was water-skiing. On 25 September 1988, a 16-year-old female died from a hemorrhage into the brain in London, Ontario. Her family gave permission to harvest the organs, and the nerves were then rushed to Toronto, and they were sewn in under the operating microscope from the buttock to the knee to replace the damaged nerve. The patient received immunosuppressive drugs according to the regimes that had been established in the years of experimental work with animals. Two years after the surgery, the patient was able to feel a pinprick on the sole of his foot for the first time since the boating accident, illustrating that the axons had successfully grown through the graft and down the nerves to the sole of the foot. The immunosuppressive drugs were then stopped and, to everyone's great relief, the clinical improvement already noted did not change, thus crowning the efforts of a large number of individuals who had begun work on this project in 1970.

The majority of the experiments were funded by the Medical Research Council of Canada. Much work is yet required, and one day it may be possible to store human nerve allografts and then use them in the complex peripheral nerve reconstructive procedures without having to resort to taking the patients' own nerves for grafting purposes, and simply using those available from the "nerve bank".