This is basic research
that means to discover all the necessary methods required to achieve a head
transplant. It is obvious that all such
protocols become immediately applicable throughout the body for many other problems.
So while I never expect
to see such a transplant seriously entertained as a surgical option, what we
learn will be fully deployed. Better,
just establishing proper nerve repair as a common procedure it worth it alone.
Most serious injuries
produce limiting nerve damage that goes untreated until the present and would
be beneficial to eliminate.
The project for the
first head transplant in man is code-named HEAVEN/GEMINI (Head Anastomosis
Venture with Cord Fusion.
The technical hurdles have now been cleared thanks to cell engineering. As
described in his paper, the keystone to successful spinal cord linkage is the
possibility to fuse the severed axons in the cord by exploiting the power of
membrane fusogens/sealants. Agents exist that can reconstitute the membranes of
a cut axon and animal data have accrued since 1999 that restoration of axonal
function is possible. One such molecule is poly-ethylene glycol (PEG), a widely
used molecule with many applications from industrial manufacturing to medicine,
including as an excipient in many pharmaceutical products. Another is chitosan,
a polysaccharide used in medicine and other fields.
HEAVEN capitalizes on a minimally traumatic cut of the spinal cord using an
ultra-sharp blade (very different from what occurs in the setting of clinical
spinal cord injury, where gross, extensive damage and scarring is observed)
followed within minutes by chemofusion (GEMINI). The surgery is performed under
conditions of deep hypothermia for maximal protection of the neural tissue.
Moreover, and equally important, the motoneuronal pools contained in the cord
grey matter remain largely untouched and can be engaged by spinal cord
stimulation, a technique that has recently shown itself capable of restoring at
least some motor control in spinal injured subjects.
* a head of a monkey was transplanted in the 1970s but the spinal cord could
not be repaired at the time
Over
the last 30 years, scientists have worked to chemically encourage regrowth. Two
chemicals, chondroitinase and FGF, show strong signs of doing exactly that--in
rats, at least. Independently, over the past three decades, each chemical has
shown some promise in restoring simple but crucial rat motor processes, like
breathing, even with entirely severed spinal cords.
Two surgeons in the field figured that a combination of the chemicals might
enhance the regrowth even more. The surgeons, from Case Western Reserve
University and the Cleveland Clinic, began by entirely severing the spinal
cords of 15 rats to ensure no independent, natural regrowth. That shut off the
rats' bladder control (a nervous system process that is especially important in
rats, since they urinate often and to mark their territory). The researchers
then injected the two growth-stimulating chemicals into both sides of the severance,
and reinforced the gap in the cord with steel wiring and surgical thread.
The indications for HEAVEN would be far-reaching (including non-brain cancer),
but, given the dearth of donors, a select group of gravely ill individuals
would be the target. This would include for instance people with some kinds of
muscular dystrophies, which prove eventually lethal and a source of major
suffering.
A Possible Head Transplant Scenario is Described
What follows is a possible scenario in order to give the reader a feel for the
whole endeavor.
Donor is a brain dead patient, matched for height and build, immunotype and
screened for absence of active systemic and brain disorders. If timing allows,
an autotransfusion protocol with D's blood can be enacted for reinfusion after
anastomosis.
The procedure is conducted in a specially designed operating suite that would
be large enough to accommodate equipment for two surgeries conducted
simultaneously by two separate surgical teams.
The anesthesiological management and preparation is outlined elsewhere. Both R
and D are intubated and ventilated through a tracheotomy. Heads are locked in
rigid pin fixation. Leads for electrocardiography (ECG), EEG (e.g., Neurotrac),
transcranial measurement of oxygen saturation and external defibrillation pads
are placed. Temperature probes are positioned in tympanum, nasopharynx,
bladder, and rectum. A radial artery cannula is inserted for hemodynamic
monitoring. R's head, neck, and one groin are prepped and draped if ACHP is
elected. A 25G temperature probe may be positioned into R's brain (deep in the
white matter), but, as highlighted, a TM thermistor should do.
Antibiotic coverage is provided throughout the procedure and thereafter as
needed.
Before PH, barbiturate or propofol loading is carried out in R to obtain burst
suppression pattern. Once cooling begins, the infusion is kept constant. On
arrest, the infusion is discontinued in R, and started in D. An infusion of
lidocaine is also started, given the neuroprotective potential. Organ
explantation in R is possible by a third surgical team.
R's head is subjected to PH (ca 10°C), while D's body will only receive spinal
hypothermia; this does not alter body temperature. This also avoids any
ischemic damage to D's major organs. R lies supine during induction of PH, then
is placed in the standard neurosurgical sitting position, whereas D is kept
upright throughout. The sitting position facilitates the surgical maneuvers of
the two surgical teams. In particular, a custom-made turning stand acting as a
crane is used for shifting R's head onto D's neck. R's head, previously fixed
in a Mayfield three-pin fixation ring, will literally hang from the stand
during transference, joined by long Velcro straps. The suspending apparatus
will allow surgeons to reconnect the head in comfort.
The two teams, working in concert, would make deep incisions around each
patient's neck, carefully separating all the anatomical structures (at C5/6
level forward below the cricoid) to expose the carotid and vertebral arteries,
jugular veins and spine. All muscles in both R and D would be color-coded with
markers to facilitate later linkage. Besides the axial incisions, three other
cuts are envisioned, both for later spinal stabilization and access to the
carotids, trachea and esophagus (R's thyroid gland is left in situ): Two along
the anterior margin of the sternocleidomastoids plus one standard midline
cervical incision.
Under the operating microscope, the cords in both subjects are clean-cut
simultaneously as the last step before separation. Some slack must be allowed
for, thus allowing further severance in order to fashion a strain-free fusion
and side-step the natural retraction of the two segments away from the
transection plane. White matter is particularly resistant to many of the
factors associated with secondary injury processes in the central nervous
system (CNS) such as oxygen and glucose deprivation and this is a safeguard to
local manipulation.
Once R's head is separated, it is transferred onto D's body to the tubes that
would connect it to D's circulation, whose head had been removed. The two cord
stumps are accosted, length-adjusted and fused within 1-2 minutes: The proximal
and distal cord segments must not be accosted too tightly to avoid further
damage and not too loose to stop fusion. A chitosan-PEG glue, as described,
will effect the fusion. Simultaneously, PEG or a derivative is infused into D's
blood-stream over 15′-30′. A few loose sutures are applied around the joined
cord, threading the arachnoid, in order to reinforce the link. A second IV
injection of PEG or derivative may be administered within 4-6 hours of the
initial injection.
The bony separation can be achieved transsomatically (i.e., C5 or C6 bodies are
cut in two) or through the intervertebral spaces. In both R and D, after appropriate
laminectomies, a durotomy, both on the axial and posterior sagittal planes,
would follow, exposing the cords. In D, the cord only has been previously
cooled. If need be, pressure in D is maintained with volume expansion and
appropriate drugs.
The vascular anastomosis for the cephalosomatic preparation is easily
accomplished by employing bicarotid-carotid and bijugular-jugular silastic loop
cannulae. Subsequently, the vessel tubes would be removed one by one, and the
surgeons would sew the arteries and veins of the transplanted head together
with those of the new body. Importantly, during head transference, the main
vessels are tip-clamped to avoid air embolism and a later no-reflow phenomenon
in small vessels. Upon linkage, D's flow will immediately start to rewarm R's
head. The previously exposed vertebral arteries will also be reconstructed.
The dura is sewn in a watertight fashion. Stabilization would follow the
principles employed for teardrop fractures, anterior followed by posterior
stabilization with a mix of wires/cables, lateral mass screws and rods, clamps
and so forth, depending on cadaveric rehearsals.
Trachea, esophagus, the vagi, and the phrenic nerves are reconnected, these
latter with a similar approach to the cord. All muscles are joined
appropriately using the markers. The skin is sewn by plastic surgeons for
maximal cosmetic results.
R is then brought to the intensive care unit (ICU) where he/she will be kept
sedated for 3 days, with a cervical collar in place. Appropriate physiotherapy
will be instituted during follow-up until maximal recovery is achieved.
More Background and History of head transplants and spinal cord repairs
There have been many studies on spinal cord repair, but many have the repair
performed after waiting for one week. It would be far easier to repair if the
repair is done right away and separation and reattachment is done in a careful
surgical way.
A brief application of the hydrophilic polymer polyethylene glycol (PEG)
swiftly repairs nerve membrane damage associated with severe spinal cord injury
in adult guinea pigs. A 2 min application of PEG to a standardized compression
injury to the cord immediately reversed the loss of nerve impulse conduction
through the injury in all treated animals while nerve impulse conduction remained
absent in all sham-treated guinea pigs. Physiological recovery was associated
with a significant recovery of a quantifiable spinal cord dependent behavior in
only PEG-treated animals. The application of PEG could be delayed for
approximately 8 h without adversely affecting physiological and behavioral
recovery which continued to improve for up to 1 month after PEG treatment.
Stem cell injections
help repair damage and restore function.
The early-stage neural
stem cells grew new axonal connections across the injury and re-established significant mobility,
something that hasn't been done before, Tuszynski said. Both rat and human
neural stem cell transplants restored function.
The stem cells improved mobility on a 21-point scale, from 1.5 after spinal
cords were severed to 7 after the treatment. The rats were treated a week after
the injury, a "clinically relevant" model for human therapy.
On March 14, 1970, a group of scientists from Case Western Reserve University
School of Medicine in Cleveland, Ohio, led by
Robert J. White, a
neurosurgeon and a professor of neurological surgery who was inspired by the
work of Vladimir Demikhov, performed a highly controversial operation to
transplant the head of one monkey onto another's body. The procedure was a
success to some extent, with the animal being able to smell, taste, hear, and
see the world around it. The operation involved cauterizing arteries and veins
carefully while the head was being severed to prevent hypovolemia. Because the
nerves were left entirely intact, connecting the brain to a blood supply kept
it chemically alive. The animal survived for some time after the operation,
even at times attempting to bite some of the staff.
Other head transplants were also conducted recently in Japan in rats. Unlike
the head transplants performed by Dr. White, however, these head transplants
involved grafting one rat's head onto the body of another rat that kept its
head. Thus, the rat ended up with two heads. The scientists said that the key
to successful head transplants was to use low temperatures.
* Effective repair of
traumatically injured spinal cord by nanoscale block copolymer micelles (Nature
Nanotechnology, 2009) These
experiments treated the damage after about ten minutes and were able to get a
lot of movement back in most cases. The damage was a crushing of the spinal
cord, so the transplant procedure would have better results because it would be
a careful separation of the spinal cord under cold conditions with immediate
application of the protectant chemicals.
Spinal cord injury results in immediate disruption of neuronal membranes,
followed by extensive secondary neurodegenerative processes. A key approach for
repairing injured spinal cord is to seal the damaged membranes at an early
stage. Here, we show that axonal membranes injured by compression can be
effectively repaired using self-assembled monomethoxy poly(ethylene
glycol)-poly(D,L-lactic acid) di-block copolymer micelles. Injured spinal
tissue incubated with micelles (60 nm diameter) showed rapid restoration of
compound action potential and reduced calcium influx into axons for micelle
concentrations much lower than the concentrations of polyethylene glycol, a
known sealing agent for early-stage spinal cord injury. Intravenously injected
micelles effectively recovered locomotor function and reduced the volume and
inflammatory response of the lesion in injured rats, without any adverse
effects. Our results show that copolymer micelles can interrupt the spread of
primary spinal cord injury damage with minimal toxicity.
Improvement in the locomotor function in the micelle-treated group was evident
by a more rapid increase of BBB scores in the first 14 days and continuation of
improvement over the following two weeks. Specifically, at 28 days post-injury,
the BBB scores were 12.5 + or minus 3.1. From a clinical perspective, an animal
with a BBB score equal to or less than 11 lacks hindlimb and forelimb
coordination, whereas a score of 12 to 13 corresponds to occasional to frequent
forelimb and hindlimb coordination. Reaching a BBB score of 12 is significant
in that it is a sign of axonal transduction through the lesion site
