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May 2011, Week 4

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Mon, 23 May 2011 00:52:41 -0400
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Curing Paralysis--Again
By R. Douglas Fields
Scientific American
May 20, 2011
http://www.scientificamerican.com/blog/post.cfm?id=curing-paralysis--again-2011-05-20

An article by Rob Stein on the front page of today's
Washington Post (May 20, 2011) announces a stunning
breakthrough treatment for paralysis that has
transformed the life of a man who was paralyzed in a car
accident.  The successful experimental treatment
involves electrical stimulation of his damaged spinal
cord through implanted electrodes. Scientists are still
not exactly sure how it works, but it does.  For one
individual reading this article, this breakthrough was
very old news-more than 27 years old.

In the early 1980's a researcher had performed similar
experiments on rats.  He had designed and hand-built
implantable microstimulators, using a simple electrical
circuit powered by a watch battery.  Then he implanted
the device into rats in which he had severed their
nerves under anesthesia.  Immediately after the surgery
was complete, he flipped a coin to determine whether to
snip the wires to the electrodes rendering the device
useless, or to leave them intact to stimulate the
growing nerve fibers.

Several weeks later when he examined the nerves
carefully with an electron microscope, the results were
striking.  There was little if any nerve regeneration in
the rats in which the stimulator had been disabled, but
the nerves in rats that had been stimulated with the
device showed remarkable healing.  Not only had the
nerve fibers regenerated, new blood vessels had formed,
infusing the tissue with nutrients, and the coating of
electrical insulation (myelin) had re-formed around the
nerve fibers.  This coating is critical for transmission
of electrical impulses.  None of the control animals
showed any myelin formation; only withered bare axon
stubs and feeble naked sprouts.  But no one ever heard
about it.

This story gives some insight into the question people
often ask about why it takes so long to bring new
discoveries in basic research to development of a
practical medical treatment, and it exposes a perplexing
dilemma.

All of this research over a quarter of a century ago was
unfunded.  It was financed by the researcher's personal
cash, which was quite modest, because he was not a
scientist with his own research lab.  He was a graduate
student living on a modest stipend.  He wrote a draft of
a scientific paper to announce the results of his
independent experiments and hired a patent attorney to
begin the process of developing a practical medical
device.   A photo of the date- stamped envelope
containing the patent application, experimental data,
and the draft of the research paper, which he mailed to
himself, is attached.

The young student may have demonstrated keen scientific
insight into a problem that costs society enormously and
brings much suffering to families and individuals, but
when he shared his results with his professor, the
student's extraordinary naivety was revealed.  None of
the research had been authorized.  The research had
nothing to do with the funded research being conducted
in the laboratory.  The university had not sanctioned
the experiments.  The proper animal study protocols had
not been submitted. The student had committed an
outrageous blunder. He had violated several legal and
ethical requirements for conducting scientific research
through his ignorance and enthusiasm.  His major
professor, legally responsible for assuring compliance
with all regulations involving research in his lab felt
betrayed and worried as he contemplated the serious
consequences.  The professor could now face charges for
having failed to adequately supervise his student to the
extent that unauthorized experiments were being
conducted in his lab.  The student's academic career was
over.

Seeing the error of his ways, the student stopped the
patent application.  He turned over his experimental
results and notes to his professor and wrote a sincere
letter of apology to him and to the university and vowed
not to pursue the research.  The transgression was
forgiven and an important lesson was learned.  Everyone
makes mistakes-especially when one is young and
inexperienced.  Today he is all the wiser for the
experience.

Now a successful scientist with his own laboratory, the
researcher kept his vow not to pursue research on
electrical stimulation for nerve regeneration.  His
research over the ensuing decades on how electrical
activity arising naturally in the brain guides the
formation of connections between neurons and stimulates
the formation of myelin on axons during development
began to reveal specific molecular mechanisms that could
explain in part how artificial electrical stimulation
could promote healing of injured nerves.  He noted with
interest over the years other researchers beginning to
experiment with electrical stimulation for treating
nerve injury, and that several of his more recent
scientific papers were cited in patent applications by
others.

There are no villains in this story, but the ending is
unsatisfying.  27 years is a long time, especially for
people suffering paralysis or other debilitating
illnesses.  It was not the quality of the science or the
motives of anyone that were faulty.  Rather, the abrupt
halt to this promising research was the consequence of a
well-intentioned system that assures proper conduct of
research.  Therein lies the dilemma. Scientific research
must be carried out responsibly.  But the system in
place to assure this outcome necessarily means that only
research that is sanctioned, supervised, and funded, can
be conducted.

History shows that it is often the young mind naively
approaching a problem from a fresh perspective that
results in the unlikely breakthrough.  But young people
are the least equipped of any to exercise their novel
ideas in scientific research.  Research that must be
sanctioned by established leaders in the field may not
be approved if it is unconventional. Would the Pope have
endorsed Galileo's experiments?  Galileo could
nevertheless perform his experiments with simple tools,
but today science has grown so complex, the
sophisticated and expensive tools and facilities
necessary to perform scientific research are well beyond
the capabilities of an individual.

Last night (before this story broke) a colleague of mine
from France was a guest in my home for dinner.  He spoke
with pride of the multi-million dollar new research
center on brain and spinal cord research that he had
spent the last three years working to establish in
Paris.  He was justifiably proud of the accomplishment,
but then he shared his impossible dream.  His wish was
that he could equip a research institute with modern
scientific equipment for the exclusive use of students.
"Why should people who are just learning their craft be
further hampered by having no equipment or being forced
to struggle with the poorest quality instruments?"  He
lamented the educational system in France, which he
likened to attending mass in which the students sat
observantly "staring like cows" at the lecturer for
enlightenment. My wife has, for the last 23 years,
taught a neuroscience research class that dispenses with
books and lectures, and replaces them with original
scientific research conducted by students.  This
involves interactions with working scientists,
presentations at scientific meetings, and even
publication in scientific journals.  The results of
empowering students in this way have been impressive.
Many are now research scientists in the most prestigious
universities in the country. But the class will not be
taught next year because of funding cuts, and instead
students will take AP Biology classes where they will be
indoctrinated with information required to pass the AP
Biology exam.

When the former graduate student read the article in the
Washington Post this morning he smiled. He had been on
the right track.  The promise of relieving the suffering
of many people struggling from traumatic spinal cord and
brain injury is on the horizon.  How do I know so much
about this him?  He is the author of this article.

About the Author: R. Douglas Fields, Ph. D. is the Chief
of the Nervous System Development and Plasticity Section
at the National Institute of Child Health and Human
Development and Adjunct Professor at the University of
Maryland, College Park. Fields, who conducted
postdoctoral research at Stanford University, Yale
University, and the NIH, is Editor-in-Chief of the
journal Neuron Glia Biology and member of the editorial
board of several other journals in the field of
neuroscience. He is the author of the new book The Other
Brain (Simon and Schuster), about cells in the brain
(glia) that do not communicate using electricity.   His
hobbies include building guitars, mountain climbing, and
scuba diving.  He lives in Silver Spring, Md.

The views expressed are those of the author and are not
necessarily those of Scientific American.

___________________________________________

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