January 2005

The Problematical Dr. Huang Hongyun

Can an experimental technique using transplanted fetal cells help paralyzed patients? Probably not. But a doctor in China is forging ahead anyway.

By Horace Freeland Judson

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Editor's note on April 17, 2006: We would like to commend Nature for its news report (fee req.) of April 13, 2006, about the claims of the Beijing neurosurgeon Huang Hongyun, which has confirmed the serious doubts raised by our correspondent in this January 2005 article.

Anesthetize the rat. Lay it belly down. Shave a patch along its spine and cut to the bone. Do a laminectomy, that is, take the bone off a short length of the back of the spine, exposing the spinal cord. Suspend a 10-gram rod above the spinal cord, at a height of 12.5 millimeters, or 25, or 50 millimeters. Let it drop.

The result will be a bruise, or more technically, a contusion, of the rat's spinal cord. The bruise interrupts nerve transmission, paralyzing some muscles and blocking sensation. The location and severity of the damage will depend on the site of the blow and the height of the drop -- and the consequent behavioral changes are reproducible. The procedure was developed in the early 1990s in the laboratory of Wise Young, a neurologist then working at New York University and now at Rutgers. He wanted to create a model for spinal-cord injury, in order to test and evaluate proposed treatments to repair the damage and restore some degree of function. Not long before, three scientists at Ohio State University had devised a rating scale for precise scoring of loss of function in spinal-cord injury. Young adapted the scale to his rat model, based on how well or poorly an injured creature could walk. In 1995, he showed that the behavioral rating varies in direct proportion with tissue damage at the injury site. In a recent conversation, he said, "This was the first behavioral outcome measure that correlated with morphological damage in the spinal cord." Although no one measure is universally accepted in spinal-cord-injury work, Young said, "This comes close."

The spinal cord is remarkably well protected, by bone and by its tough outer layer, the dura. In humans, only about 10 percent of spinal-cord injuries, caused by mishaps like a bullet through the spine, interrupt the cord completely. Ninety percent are contusions. Nerves in the adult central nervous system, including the spinal cord, do not spontaneously regenerate. Some nerves in the peripheral system, however, can -- importantly, in the presence of Schwann cells, a type of cell that provides an environment favorable to new growth of nerve axons. Many attempts have been made to transplant such cells into damaged spinal cords, to promote regeneration, but they have all failed.

Enter olfactory ensheathing glial cells -- bearing the hope of a way to fix, or at least to ameliorate, spinal-cord injuries. In 1984, Ron Doucette, at the University of Saskatchewan, described a new kind of cell, which he had found in the olfactory nerve and the olfactory bulb. The olfactory nerve is the only central-nervous-system nerve that continually regenerates throughout adult life. It is made up of neurons that arise in the mucous tissue of the nose and run the short distance to the olfactory bulb, one of the most primitive parts of the brain.

We sniff substances all the time that are toxic to these neurons, which die and must be replaced. New ones are constantly being generated. They send axons up the olfactory nerve to establish fresh connections to the bulb. Doucette's new-found cell produces a particular protein that marks it as a glial cell -- a class of support cells, which include Schwann cells, that surround neurons. The surface of Doucette's cell carries what are called cell-adhesion molecules, which attract growing axons. In the years after his discovery, Doucette isolated these cells and learned to grow them in tissue culture. He found that they wrap around axons and promote their growth: hence the name, olfactory ensheathing glial cells. In 1990, Doucette proposed that they are the principal reason the olfactory nerve can regenerate. Then and today, he has been pursuing how exactly Schwann cells and ensheathing cells do what they do.

The exciting question was whether the glial cells might encourage regrowth of spinal-cord neurons. Several scientists jumped on it, conspicuously Almudena Ramón-Cueto of the Universidad Autónoma de Madrid in Spain and Geoffrey Raisman at the National Institute of Medical Research in London .

The Problematical Dr. Huang Hongyun

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