Papers published today detailing the spinal cord repair technique applied to the dog have prompted other scientists to express concerns over the work. “These papers do not support moving forward in humans,” says Jerry Silver, a neuroscientist at Case Western Reserve University in Ohio.
In a series of three papers, all edited by Canavero for the journal Surgical Neurology International, researchers in South Korea and the US claim that a chemical called polyethylene glycol, or PEG, may help reconnect a severed spinal cord.
C-Yoon Kim at Konkuk University in Seoul and his team – who have been working closely with Canavero – severed the spinal cord of 16 mice. They then injected PEG into the gap between the cut ends of the spinal cord in half of the mice, while the rest were injected with saline. After four weeks, they report that five of the eight mice in the PEG group had regained some ability to move, compared with none of the control group. The other three PEG-treated mice died, as did all those in the control group.
Even better spinal cord repair treatment with graphene nanoribbons
A team at Rice University in Houston, Texas, has been working to develop a better version of PEG. Hearing about Canavero’s plans to use the solution in a human head transplant, the team believed it could improve it by adding graphene nanoribbons – an electrically conductive material that acts as a scaffold that neurons can grow along.
“My motivation is spinal cord repair. If this works, it’s going to have huge ramifications for spinal injuries,” says James Tour, who is part of the Rice team. “But we thought, if you’re going to be working towards a head transplant, you’re going to need this, so let us help you.”
In a final experiment, the South Korean team tested the original PEG in a dog immediately after it was given a near-complete cervical (neck) spinal lesion. Visual inspection suggested more than 90 per cent of its spinal cord had been severed – similar to what is seen in people who receive stab wounds to the spinal cord.
The following day, the dog was completely paralysed, but after three days, the team reports minimal movement in all four limbs. After two weeks, the dog was able to drag its hind limbs by its torso and forelimbs, and during the third week, it was able to walk. The team claims that the dog began to grab objects, wag its tail and resume a normal life. There was no control in the experiment.
Human head transplant scheduled for Dec, 2017
The world’s first head transplant patient has scheduled the procedure for December 2017. Valery Spiridonov, 30, was diagnosed with a genetic muscle-wasting condition called Werdnig-Hoffmann disease, and volunteered for the procedure despite the risks involved. Nextbigfuture has covered the proposed full human body [aka human head transplant] transplant procedure several times. The background information and science behind the procedure is below.
Dr. Sergio Canavero, an Italian neurosurgeon, will perform the procedure on Spiridonov. The procedure is expected to last up to 36 hours, and it will require Spiridonov’s head be cooled as well as the donor’s body. Canavero calculates it will take two years to plan and prepare for a successful procedure. The surgery will be done once the doctor and the experts are 99 percent sure of its success.
Italian surgeon Sergio Canavero announce a project perform a human head transplant at a keynote lecture at the American Academy of Neurological and Orthopaedic Surgeons annual conference this June.
He believes the patient would be able to speak in his own voice upon waking and that walking could be achieved within a year. "If society doesn't want it, I won't do it," Canavero says. "But if people don't want it in the US or Europe, that doesn't mean it won't be done somewhere else.
Most other surgeons do not believe the procedure will be successful.
New Scientist reports that Xiao-Ping Ren of Harbin Medical University in China recently showed that it is possible to perform a basic head transplant in a mouse. Ren will attempt to replicate Canavero's protocol in the next few months in mice, and monkeys.
CNS Neuroscience and Therapeutics - Allogeneic Head and Body Reconstruction: Mouse Model
Ren's approach, pioneered in mice, involves retaining the donor brain stem and transplanting the recipient head. Our preliminary data in mice support that this allows for retention of breathing and circulatory function. Critical aspects of the current protocol include avoiding cerebral ischemia through cross-circulation (donor to recipient) and retaining the donor brain stem. Successful clinical translation of AHBR will become a milestone of medical history and potentially could save millions of people. Ren's mouse experiment confirmed a method to avoid cerebral ischemia during the surgery and solved an important part of the problem of how to accomplish long-term survival after transplantation and preservation of the donor brain stem.
Head Transplant Procedure
* The sharp severance of the cervical cords (donor's and recipient's), with its attendant minimal tissue damage
* The exploitation of the gray matter internuncial sensori-motor "highway" rebridged by sprouting connections between the two reapposed cord stumps. This could also explain the partial motor recovery in a paraplegic patient submitted to implantation of olfactory ensheathing glia and peripheral nerve bridges: A 2-mm bridge of remaining cord matter might have allowed gray matter axons to reconnect the two ends
* The bridging as per point 2 above is accelerated by electrical SCS straddling the fusion point
* The application of "fusogens/sealants": Sealants "seal" the thin layer of injured cells in the gray matter, both neuronal, glial and vascular, with little expected scarring; simultaneously they fuse a certain number of axons in the white matter.
During CSA, microsutures (mini-myelorrhaphy) will be applied along the outer rim of the apposed stumps. A cephalosomatic anastomosee will thus be kept in induced coma for 3-4 weeks following CSA to give time to the stumps to refuse (and avoid movements of the neck) and will then undergo appropriate rehabilitation in the months following the procedure.
In addition, the immunosuppressant regime that will be instituted after CSA is expected to be pro-regenerative
Figure 1: (a) Longitudinal cut along a primate spinal cord depicting the internuncial system (gray matter motor highway) and the nano-size of the proposed severance (left). The red circle on the right side of this panel is the pyramidal tract, shown in two exploded views of a sharply transected cord (middle right) and of the cord in the vertebral canal (lower middle right). (b)Visualization of the severed pyramidal tract. The uppermost image depicts a motor neuron in the cortex sending forth the axonal prolongation. Middle panel: The pyramidal tract (red) and a portion of its severed axons. Lower panel: The sharply severed axonal extensions (adapted from Laruelle 1937 and several images in the public domain)
The project for the first head transplant in man is code-named HEAVEN/GEMINI (Head Anastomosis Venture with Cord Fusion.
I covered the internet and news reactions to the 2013 discussion of technical feasibility of head transplants.
I consider the 2013 proposed procedure in the context of organ donation and xenotransplantation.
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.
Surgical Neurological International - HEAVEN: The head anastomosis venture Project outline for the first human head transplantation with spinal linkage (GEMINI)
* a head of a monkey was transplanted in the 1970s but the spinal cord could not be repaired at the time
* Spinal cords have been regrown in rats.
* In 2000, guinea pigs had spinal cords surgically cut and then protected with PEG chemical (like what is proposed here) and they had over 90% of spinal nerve transmission restored with a lot of mobility and function restored
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 Cleveland clinic has the full description of the rat spinal cord repair.
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.
In 2000, there was immediate recovery from spinal cord injury through molecular repair of nerve membranes with polyethylene glycol. (10 pages) Immediate and full (over 90%) recovery from a severed spinal cord was performed in adult guinea pigs with the application of one of the chemicals proposed in the human head transplant project.
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.
Rats with spinal cord injuries and severe paralysis are now walking (and running) thanks to researchers at EPFL. Published in the June 1, 2012 issue of Science, the results show that a severed section of the spinal cord can make a comeback when its own innate intelligence and regenerative capacity is awakened.
In 1959, China announced that it had succeeded in transplanting the head of one dog to the body of another twice.
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
Ethical full body donation
The need for organ donors has never been greater. Presently, there are more than 110,000 people on the national waiting list who need a life-saving organ transplant.
Organ donations in the USA are made after a donor has been declared brain dead.
I do not see the argument that donating all of the body of a brain dead person to another recipient is unethical. It seems that careful policy would make it as ethical as organ donation from someone deceased.
Experiments on animals for body transplant also seems ethical as it would be work to lead to clinical treatment.
Data on the number of US organ transplants in each year.
The number of organ donors ranges from about 6 to 34 donors per million people depending upon country. There are plans to get up to 40 donors per million people. The number of organ transplants is higher because one donor could provide organs for multiple transplants.
There has been work to make genetically modified pigs as a source for human heart transplants.
Xenotransplantation is the transplantation of living cells, tissues or organs from one species to another. There have been a few dozen xenotransplantations into humans.
So how far could an ethical boundary go ?
Could genetically modified pigs be used for body donation to keep someone's head alive for extended periods of years ?
Could you transplant someones head, arms and legs to the genetically modified pig ?
Could genetically modified chimps or gorillas be mass produced for whole body donation ? The immune system would be modified for compatibility but other aspects would remain to prevent it becoming too human as a source.
There has been research on giving mammals improved regeneration and self-healing capabilities like those that exist in salamanders. Regeneration and healing genetic enhancement has been done mainly in mice. It could be adapted to chimps, gorillas and pigs. It would be immune and healing steps to enhance the level of recovery of the spinal cord and acceptance of the transplant.
SOURCES- New Scientist, FAS, Wikipedia, Cleveland Clinic, University of Purdue, transplant living