Could Frankenstein be a reality?

Nearly two centuries ago, constructing a human life was merely a thought of
imagination. The legendary novel Frankenstein by Mary Shelley was the novel that
introduced this idea to the world. Recreating a personʼs spine, thus reconnecting the
brain back to the body, is an idea of the past and reality of our future. Dr. John D. Houle
of Drexel University in Philadelphia, Pennsylvania, is on the cutting edge of spinal
regeneration in animals. The research at hand is of utmost importance because it will
readily be applied to us when such a discovery allows the leap from animal to human.
Dr. Houle began his spinal regeneration research interest at Purdue Universtiy while
receiving his PhD. He then moved on to the University of Florida and the University of
Saskatchewan to complete his post-doctoral fellowship. His time spent at these
institutions, lead him to become a faculty member for the Department of Neurobiology
and Developmental Sciences.
These experiences has given him the basis for his
research at Drexel University, where he resides as a
Professor within the Department of Neurobiology and
Anatomy. His focus has remained on correcting
spinal lesions (injury) in mice for many years. He is
funded by the National Institute of Neurological
Disorders and Stroke (NINDS). When a spine has a
lesion, the signals from the brain to the body are
relayed a bit slower or possibly not at all. It is
somewhat similar to that of a short in an electrical
circuit. Dr. Houle set out to solve this dilemma, and like everyone else has had ups and
downs.
A spine consists of many components as shown in this picture below. The gray
matter is in the center of the cord, in the shape of an “H.” This gray matter is crucial to
the development of new nerve tissues and axons. The PNG that is created travels
from a C3 lesion site to a C5 hemisection and the grafted nerve must be able to connect
grey matter tissues in order for a neural circuit to work correctly.

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In order to do this, Dr. Houle designed an idea that would basically create another route
for the “signal” to be transfered. In other words, he went around the lesion site and
through the “gray matter” of the spine. A rather involved experiment of his consisted of
inducing spinal lesions to lab mice, and then testing this “round about” method on them.
The mice were tested for their function after the procedure by certain tests of physical
and mental testaments. To begin, an enzyme by the name of Chondroitinase ABC
(ChABC) was used to cleave side chains of glycosaminoglycans (GAGs). GAGs are
molecules that are known to inhibit the growth of axons. GAG is any group of
molecules that are components of connective tissue. They consist of polypeptides with
amino groups attached. In addition they are a member of the chondroitin sulfate
proteglycan family. A proteoglycan is a compound that contains a protein attached to a
glycosaminoglycan. These proteglycans are known to be notorious for their repulsive
features towards scar-associated ExtraCellular Matrix (ECM) molecules, meaning a
scar will not likely form as they do for the majority of the time. What Dr. Houle set out to
do was to skip the lesion site by regeneration of axons using a Peripheral Nerve Graft
(PNG) from the mouseʼs tibia. In order to stimulate re-growth from the lesion sites,
ChABC was administered in measured doses to the ends where the lesion sites were.
 In this figure the upper left illustration is a visual of exactly what the PNG is doing and
what it looks like within the spine. The space the PNG is passing through is known as
the grey matter as shown in the previous figure. This allows the lesion site to be passed
over and the signal “circuit” to be completed, thus allowing function to be reinstated.

The results were interpreted by using immunocytochemical staining after the PNG had
begun to grow. The stains were used to tag axonal re-growth and the spinal nerve cells.
For a spinal cord to fully function, the nerve cells and the axon cells must come in
contact, hence the point of this experiment. The PNG is the nerve cells growing from
one axonal lesion site out into the gray matter of the spinal cord tissue, outside the
axonal cell tissue, and is then connected to the to the other lesion site. The PNG must
do two things: first grow around the lesion site and connect both lesion ends; second,
the PNG must grow into both ends of the lesion site connecting with axonal cells, thus
completing the “circuit”; and third, this graft must obtain normal function for the mouse,
movement, behavior, etc. This brings us to the last testing stage within this experiment,
the movement and behavior of the mice after the PNG had been completed. The tests
done were just basic exercises, such as walking across a rope, or the cylinder test.
However, since in this situation the tibial nerve was used as the graft nerve (PNG) then
the right hindlimb of all subject mice were hindered. None the less, each test was
conducted with this in mind, and done unbiasedly. Examples of these tests include a
rope walk and a wheel walk. This experiment contained much detail, science and
phenomena that have yet to be explained.
 Dr. Houle has found many useful techniques and many are still being discovered.
He continues to do his research at Drexel University to this day, and will continue to
uncover more possibilities to hopefully one day solve the problem of spinal regeneration
in spinal injury. Philadelphia, Pennsylvania has hosted this world renowned research
and is honored to have such an accomplished individual so close to home.

References:

1. Houle JD, Tom VJ, Mayes D, Wagoner G, Phillips N, and Silver J.(2006) “Combining
an Autologous Peripheral Nervous System “Bridge” and Matrix Modification by
Chondroitinase Allows Robust, Functional Regeneration beyond a Hemisection Lesion
of the Adult Rat Spinal Cord.” The Journal of Neuroscience. http://www.jneurosci.org/
cgi/content/short/26/28/7405

2. Houle JD, Ziegler MK.(1994) “Bridging a complete transaction lesion of adult rat
spinal cord with growth factor-treated nitrocellulose implants.” Journal of Neural
Transplant Plast. Pp.115-124. http://www.ncbi.nlm.nih.gov/sites/entrez?
Db=pubmed&DbFrom=pmc&Cmd=Link&LinkName=pmc_pubmed&LinkReadableName
=PubMed&IdsFromResult=2565283&ordinalpos=5

3. Shelley, Mary. Frankenstein. Published in France. 1818.

4. Picture of John D. Houle, PhD. http://neurobio.drexel.edu/houleweb/houle.html

5. Department of Neurobiology and Anatomy, Drexel University. John D. Houle.

“Neurotransplantation Strategies to Promote Structural and Functional Recovery after
Spinal Cord Injury.” 2005.

6. Drexel University image. Philadelphia, PA.

http://www.drexel.edu/images-core/at-a-glance-enlarge.jpg

7. National Institute of Neurological Disorders and Stroke. “Spinal Cord Injury:

Emerging Concepts.” 22 June, 2007. http://www.ninds.nih.gov/news_and_events/
proceedings/sci_report.htm#Anatomical

8. The Dana Foundation. “Spinal Cord Injury-Harnessing Regeneration and Immune

Defenses.” Brenda Patoine. http://www.dana.org/news/publications/detail.aspx?
id=4272

9. “Spinal Cord Injury Research.” Mayo Clinic. http://discoverysedge.mayo.edu/

spinal_cord_injury/index.cfm

10. Monaghan JR, Walker JA, Page RB, Srikrishna P, Beachy CK, Voss SR. “Early
gene expression during natural spinal cord regeneration in the salamander.” The
Journal of Neurochemistry, pp. 27-40. 2007.