From that article:

Until that time it had been assumed that we are born with a fixed number of nerve cells, and the best that we can do is to try to prevent losing them to alcohol, or to boxing, or to Alzheimer's or Parkinson's diseases. That is still very largely how we understand things. But in the 1960s, Pasquale Graziadei, a former student of JZ at University College London, was working in Florida. He had shown that in one part of the nervous system – and so far in the only one that we know of – nerve cells are continually replaced throughout adult life.17

This is the olfactory system, the part of the nervous system lying in the upper nasal lining and carrying the sense of smell. And this process of continual renewal reflected the persistence of an embryonic property, the property of cell division. So here, in the adult, was a fount of unending youth. And maybe a source of pathway cells? But that's hindsight. We're racing ahead. The idea of transplanting pathway cells from the olfactory system took quite a bit longer, quarter of a century to be precise.

The fibres arising from the newly formed olfactory neurons pass through the skull and terminate in the olfactory bulbs. Moreover, Graziadei et al18 had shown that if an olfactory bulb was removed, the olfactory nerve fibres would continue to grow through the cranial cavity until they reached the next area, the frontal cortex, which they then entered and made connections there. So the olfactory nerve fibres have the property of entering parts of the brain which do not normally receive them. But how do they do it?

Graziadei's observation passed practically unnoticed. It was only some 10 years later, and after his untimely death, that the significance of his work began to percolate into my consciousness. Based on the pathway hypothesis, I had speculated that the ability to grow depended not on the nerve fibres, but on the presence of specialised pathway cells. Finally, in 1985,19 I first described a type of pathway cell, unique in structure and arrangement, and found only in the primary olfactory pathway. This cell is now called the olfactory ensheathing cell.20

Some years later Doucette in Canada described how to obtain olfactory ensheathing cells in tissue culture of samples taken from the adult olfactory system.21 And with this knowledge the stage was set for us to begin to transplant them. In doing this, we were carrying out a transplant not only in space, but – so to speak – in time, from a part of the body which retains embryonic characteristics into a part of the body which has lost them.

The results were beyond our dreams.22 The cells survived transplantation, and they opened up a pathway (Figure 4), which allowed the growth of severed nerve fibres. The transplanted cells formed a bridge conveying the regenerating nerve fibres across the injury (Figure 5). They had repaired the roadway. A bridge had been thrown across the washed out motorway and the cars were driving across it. But most important – they restored function (Figure 6).


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I will never forget one early morning, sometime in the dead period between Christmas and New Year, when for some reason I decided to examine the rats at about 0200 hours. On the way to the animal house I remember my breath coming out as steam in the frozen night air. The test was for the rat to retrieve a piece of food I offered it. It was a rat which had a unilateral lesion of the left corticospinal tract at the upper cervical level. Since the time of lesioning, it had never used its left paw for retrieval. The damage was on the left, and the cultured olfactory ensheathing cells had been transplanted into the lesion.

Then I could hardly believe my eyes. The rat put its left paw forward, just tentatively then paused. I was amazed. But I think the rat was equally amazed. For a moment we looked at each other in surprise. Then it went on and took the food. And at that moment I knew the breakthrough had come. It was a moment that occurs once in a lifetime – if you are lucky. Many years followed. Repeat, extend, confirm. We examined three systems in the rat. First the animals recovered the ability to retrieve pieces of food with the forepaw of the operated side. Second they learned to recover the use of the paw for climbing. And third the transplants restored the breathing ability to the diaphragm of the operated side.24

The ability to engineer the re-entry of nerve fibres into the spinal cord is a proof of principle, or rather of principles. These principles are:

1. There exist, in all of our bodies, adult stem cells which can be used to generate reparative tissues. No need to resort to embryonic cells. No need to cross any immune barriers or use any immunosuppressive drugs. The patient can be his or her own donor.
2. Severed nerve fibres can be reconnected in an adult spinal cord.
3. Lost functions can be restored.

In 1974, I moved from the Department of Human Anatomy in Oxford to the National Institute for Medical Research at Mill Hill, where the Medical Research Council supported my research work for many years. This gave me the opportunity to work out the basic methods for transplantation of cultured olfactory ensheathing cells, and to study the reconnection and functional repair in rats. But still I was far from having these dreams applied. It was only in 2005, with the move of the research team to the Institute of Neurology in Queen Square, that we finally had access to the neurosurgeons who were both willing and also had the opportunity to plan for the clinical application of olfactory ensheathing cell transplants.

We already have permission for the first preliminary safety study, which is scheduled for this year, 2006. Our first attempt will be to repair avulsed dorsal roots.25 Success would open the way to evolve techniques for repairing larger ('transverse') spinal cord injuries, as well as brain injuries resulting from some of the most severe types of stroke, those affecting descending motor pathways, and blindness and deafness caused by damage to the fibres of the nerves of vision and hearing.

I hope our team can contribute to some of these. But we need to be realistic. We have not learned how to repair a twelve-lane metalled motorway. If we are lucky we will be able to throw a plank over where a stream crosses a field path. We have not yet invented tarmacadam or reinforced concrete. We do not know how to build cantilevered bridges. There will be many more developments needed for the motorway engineers of the future.

But after all, in the end our success is not that we have done this, but that we have opened a door through a wall that was impenetrable. And repair of injuries is only one aspect of the concept of plasticity. Evolution did not develop plasticity as a potential method for repairing injuries, a method which would lie unachieved and dormant for millions of years until someone thought of transplanting olfactory ensheathing cells. For me, the concept of plasticity opened a much wider significance.

After all, what is the function of the brain? It is not claws and teeth but the brain that is the principal organ of evolution. The battle is to the wily, not to the strong. If we ask what is the function of the brain, the usual answers may be to move the hands, to see, to hear. But these are pretty lowly, mechanical functions, something a robot with a computer might imitate. But look around! Everything we see around us is a creation of the human brain. Nothing is of nature. We made or modified it all, even the sky itself bends to our wills however blind to the consequences. That is the important function of the brain. And it was not the brain of an individual, or of one time, but of an organised society of brains, acting over a long period.

The function of the brain is plasticity, the ability to change, not to respond the same way twice. If it's good, go for more. If it's bad avoid it. Explore, be curious, remember, learn, build, form concepts. And pass them on to future generations. Those are the important functions of the human brain. Those defined our brains. And all of them involve plasticity. The ultimate expression of plasticity is history itself, the ever changing.

This is meant to be an inaugural lecture, but I wonder what I am inaugurating. So large a part for me personally is a valedictory. But all our activities in the end are only an inauguration of what will follow. Research, knowledge, do not belong to anyone. Like the earth itself, they belong to no one. Rather we belong to them. And human evolution is social evolution. The advances come not from a person, but from a team. It is a joy for me to see ideas floated out among our little team, like rose petals in a whirlpool, finally forming a pattern that no single one of us alone could have framed. And so this article uses the word 'I' where it means 'we.' If I pick out Ying Li and Daqing Li, who have given 20 years to this project, and who have changed their homeland to do it, it is not to detract from the many contributors and supporters along the way, who are too numerous and too varied to acknowledge.

This article is not intended to be a review of the wider field of neural regeneration (of which there are many available26), nor to document the work on repair by transplantation of cells. Its purpose is only to record, with the inevitable distortions, omissions, and creations of fallible memory, some of the glimpses of the mysterious countryside seen from the rather cloudy windows of a fast moving train, a personal journey.

http://www.nature.com/sc/journal/v44.../3101948a.html