Ramón-Cueto first tried cutting the peripheral nerves of rats at the point, called the spinal root, where they connect with the spinal cord. Such injuries are crippling. Normally the nerves will not grow back into the spinal cord. She then transplanted some of the creatures’ own olfactory ensheathing glial cells into the region of the root, and in 1994, she claimed that this allowed the nerves to regenerate their connections. She then went to work with Mary Bunge of the Miami Project to Cure Paralysis, which is at the University of Miami. Bunge’s main approach has been to graft Schwann cells into rats’ spinal cords, bridging spinal lesions, and then to try various measures, including drugs in different combinations, to get them to grow. In 1998, she and Ramón-Cueto injected adult-rat olfactory ensheathing glial cells into the areas at each end of the Schwann bridges. They reported that six weeks after the combined graftings, spinal-cord axons were growing through the Schwann cell bridges and beyond – and that the ensheathing cells had migrated, accompanying growing axons through and alongside the Schwann bridges.
Raisman, meanwhile, was also experimenting with olfactory ensheathing glial cells. In 1985, he had suggested that these cells had special properties that enabled them to repair central-nervous-system neurons. Now, in a clever experiment, he used a thin electrode to burn through rat spinal cords on one side only, at a point that left the creatures able to use only one forepaw. Before the operation, he had trained the rats to reach through a hole for pellets of food with their forepaws, using one or the other with equal facility; afterwards, they were unable to reach with the affected limb but could use the other normally. He then transplanted into the spinal lesions a mixture of cell types, including olfactory ensheathing glial cells. In 1997, Raisman and colleagues reported in Science that as early as ten days after the transplants, spinal-cord axons sprouted and grew across the lesions. Two to three months after the transplants, of a group of seven rats, four were able to use either forepaw as adeptly as normal rats. Dissection showed that these four had regrown spinal-cord axons across the lesions.
In 2000, after returning to Spain, Ramón-Cueto published a paper in the journal Neuron asserting that when she transected the spinal cords of rats and injected olfactory ensheathing glial cells into the lesions, many of the rats recovered some locomotor function. The degree of regeneration and recovery was slight, and some raised questions about exactly how she did the tests. Yet the paper had impact.
The pressure is now intense to get to clinical trials. The United States alone has on the order of 200,000 patients with spinal-cord injuries. (Their plight was dramatized by Christopher Reeve, the quadriplegic Superman and spinal-cord campaigner, who died on October 10, 2004.) Raisman is pushing toward trials, as is Ramón-Cueto. In June 2003, Raisman told the BBC, “My guess is we are probably two to three years away. It could be less.” A group in Brisbane, Australia, led by Alan Mackay-Sim, has duplicated the rat experiments with ensheathing cells and is at the stage of exploratory clinical trials; Carlos Lima, from the Egaz Moniz Hospital in Lisbon, has treated a small number of patients. Yet extreme caution is obviously necessary: the procedure raises great scientific, medical, regulatory, and ethical problems. In a recent telephone conversation, Doucette emphasized repeatedly that the basic physiology is still not understood. “Just putting the cells in and saying, ‘Oh, great, we’ve got some functional recovery,’ and then moving on to the next step, to me isn’t satisfactory. I want to know how it happened. Why. And how you can control it,” he said. He went on: “My view is that I think we’re probably five, ten years away. In terms of being at a stage where I’m confident we know enough about what’s going on.”
Enter Dr. Huang Hongyun.